Publications by authors named "Hamid Akbari Javar"

37 Publications

Potential of chitosan/alginate nanoparticles as a non-viral vector for gene delivery: Formulation and optimization using D-optimal design.

Mater Sci Eng C Mater Biol Appl 2021 Sep 16;128:112262. Epub 2021 Jun 16.

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran. Electronic address:

Chitosan/alginate (Chi/Alg) nanoparticles as a non-viral vector for the Smad4 encoding plasmid were optimized utilizing D-optimal design based on the nanoparticles/plasmid ratio, Chi/Alg MW, and preparation method type. Following the optimization and validation of the best formula, morphology studies and FTIR measurements were performed to evaluate the optimized Chi/Alg/S NPs. Toxicity (MTT assay) and transfection studies were performed for the best formula in comparison with Lipofectamine 2000, and Polyethyleneimine (PEI) and evaluated using Green Fluorescence Protein (GFP) assay, Flow cytometry, and RT-PCR. The model predicted a particle size of 111 nm, loading efficacy (LE) of 43%, cumulative release (CMR) of 39%, the ζ-potential of +50 mV, and PDI of 0.13. The predicted point condition was as follows: NP ratio = 13, Chi/Alg MW ratio = 2.35, and preparation method type = 1. Microscopic findings revealed that the shape of nanoparticles was spherical. The Chi/Alg/S nanoparticles showed no toxicity and transfection efficacy of 29.9% was observed in comparison with Lipofectamine (35.5%) and PEI (30.9%).
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http://dx.doi.org/10.1016/j.msec.2021.112262DOI Listing
September 2021

A comparative pharmacokinetic study of a novel sustained release danofloxacin formulation and the conventional product in rabbits.

Vet Res Forum 2021 15;12(2):253-257. Epub 2021 Jun 15.

Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Sustained release drug formulations are frequently developed to reduce dosage frequency and to improve outcomes of drug therapy. This study evaluates the pharmacokinetic (PK) parameters of a novel injectable danofloxacin (DANO) formulation in comparison with a conventional product in an animal model. A recently synthesized DANO formulation, prepared by incorporation of DANO-loaded mesoporous silica nanoparticles in liposomes and integration of liposomes in chitosan and β-glycerophosphate solution (lipogel) along with the conventional DANO product were injected subcutaneously (SC) in rabbits. Blood samples were collected at specific time points and DANO concentrations in plasma samples were measured. The PK parameters including maximum concentration (Cmax), time to reach Cmax (Tmax), area under the concentration versus time curves (AUC), area under the first moment concentration-time curve (AUMC) and mean residence time (MRT) were studied by non-compartmental analyses. The values of MRT (156.00 ± 20.00 hr), AUC (15.30 ± 3.00 µg mL per hr) and Tmax (4.70 ± 1.60 hr) for lipogel formulation were higher than those of the conventional product (8.50 ± 3.60 hr, 3.70 ± 2.00 µg mL per hr and 0.80 ± 0.26 hr, respectively). However, Cmax values for lipogel formulation (0.41 ± 0.15 µg mL) were significantly lower than those of the conventional drug product (0.68 ± 0.09 µg mL). It was concluded that the novel DANO lipogel effectively slowed down the drug absorption and the incorporation of liposomes in hydrogel could be a useful approach to maintain the therapeutic drug level for a longer period; however, more studies are needed in this field.
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http://dx.doi.org/10.30466/vrf.2019.105313.2504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328252PMC
June 2021

The effect of coronavirus (COVID-19) pandemic on medical sciences education in Iran.

J Educ Health Promot 2021 20;10:136. Epub 2021 May 20.

Department of Emergency Medicine, Clinical Research Development Unit, Yasuj University of Medical Sciences, Yasuj, Iran.

Background: COVID-19 has a great impact on medical sciences education. Some researches have been conducted on the effects of the COVID-19 pandemic on medical sciences education in the world. The aim of this study was to identify the effects of this disease on medical sciences education in Iran.

Materials And Methods: This futures study research was carried out using the future wheel method in Iran's University of Medical Sciences in the spring of 2020. A semi-structured interview was also conducted on the vice chancellors of medical sciences universities, faculty presidents, faculty vice chancellors, faculty members, medical education specialists, and university students, who were purposefully identified. The interview continued until achieving data saturation. Analysis of the interviews was performed by MAXQDA version 10 software.

Results: The effects were presented at three levels including primary effects, secondary effects, and third effects. In addition, 16 primary effects, 51 secondary effects, and 24 tertiary effects were recognized. One primary effect of the coronavirus (COVID-19) pandemic on medical sciences education in Iran was fear, stress, and anxiety among students and faculty members as well as staffs to get the disease. In addition, rumor was circulated concerning the infection of some people, thus, there was a need for holding courses regarding stress management and rumor management. One secondary effect of the coronavirus (COVID-19) pandemic on medical sciences education in Iran was allocation of a number of educational hospitals to the referral hospitals of COVID-19. One tertiary effect of the coronavirus (COVID-19) pandemic on medical sciences education in Iran was increasing the number of virtual courses.

Conclusions: The most important effect of this disease on medical sciences education is the postponement of practical and apprenticeship classes, and consequently the increased length of the academic term that leads to delay in the students' graduation, which can reduce the workforce. On the one hand, this disease causes death of a number of students, educational and medical staffs, and faculty members, as well as reduces the workforce. Also, lengthening the recruitment of faculty members will add to this challenge. In this regard, there is a need to plan to compensate for the shortage of required human resources.
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http://dx.doi.org/10.4103/jehp.jehp_817_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224502PMC
May 2021

Design and In Vitro Evaluation of a Slow-Release Intraocular Implant of Betamethasone.

AAPS PharmSciTech 2021 Jun 10;22(5):174. Epub 2021 Jun 10.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Posterior eye diseases are a common cause of vision problems in developing countries, which have encouraged the development of new treatment models for these degenerative diseases. Intraocular implants are one of the drug delivery systems to the posterior region of the eye. Using these implants, the blood-eye barrier can be bypassed; the complications caused by repeated in vitro administrations can be eliminated, and smaller amounts of the drug would be used during the treatment process. Meanwhile, biodegradable implants have received more attention due to their biodegradable structure and the lack of need for re-surgery to remove the rest of the system from the eye. The aim of this study is to employ biodegradable implants composed of polyethylene glycol (PEG) and 3-hydroxybutyrate-co-3-hydroxyvalerat (PHBV) to deliver betamethasone to the back of the eye in the treatment of retinopathy. PHBV polymer has been selected as the main polymer with a certain ratio of drug to polymer for fabrication of enamel and different amounts of PEG with three molecular weights used as pore generators to control drug release over a period of time. Based on the analysis of the results of differential scanning calorimetry (DSC) and FTIR spectroscopy, none of the polymers were degraded in the temperature range of the manufacturing process, and among betamethasone derivatives, the best option for implant preparation is the use of its basic form. Drug release studies over a period of three months showed that implants containing PHBV HV2% and PEG 6000 had a more appropriate release profile.
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http://dx.doi.org/10.1208/s12249-021-02048-0DOI Listing
June 2021

Preparation, Statistical Optimization and Characterization of Propolis-Loaded Solid Lipid Nanoparticles Using Box-Behnken Design.

Adv Pharm Bull 2021 Feb 20;11(2):301-310. Epub 2020 Jun 20.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Propolis is a resinous material obtained by honeybees with many biological and pharmacological properties which can be used for treatment of various diseases. Current study aims to formulate and characterize propolis-loaded solid lipid nanoparticles (SLNs) carrier system. The prepared SLNs, composed of glyceryl monostearate (GMS), Soy lecithin, Tween 80 and polyethylene glycol 400 (PEG 400), were fabricated employing solvent emulsification-evaporation technique. In addition, the impact of several variables including concentration ratios of GMS/Soy lecithin and PEG 400/Tween 80 along with emulsification time were evaluated on the size, polydispersity index (PDI) and zeta potential of particles. SLN formulations were optimized using Box-Behnken design. The particles were freeze dried and morphologically studied by scanning electron microscopy (SEM). The in-vitro release profile of propolis entrapped in the optimized nanoparticles was investigated. The mean particle size, PDI, zeta potential, entrapment efficiency (EE) and loading efficiency (LE) of optimized propolis-loaded SLNs were found to be 122.6±22.36 nm, 0.28±0.06, -26.18±3.3 mV, 73.57±0.86% and 3.29±0.27%, respectively. SEM images exhibited nanoparticles to be non-aggregated and in spherical shape. The in-vitro release study showed prolonged release of propolis from nanoparticles. The results implied that the proposed way of SLN preparation could be considered as a proper method for production of propolis loaded colloidal carrier system.
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http://dx.doi.org/10.34172/apb.2021.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046400PMC
February 2021

Fabrication, Optimization, and In Vitro and In Vivo Characterization of Intra-vitreal Implant of Budesonide Generally Made of PHBV.

AAPS PharmSciTech 2020 Nov 9;21(8):314. Epub 2020 Nov 9.

Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Science, Tehran, Iran.

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R = 0.9861, p ˂ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery. Grapical abstract.
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http://dx.doi.org/10.1208/s12249-020-01828-4DOI Listing
November 2020

Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery.

Int J Nanomedicine 2020 29;15:8345-8356. Epub 2020 Oct 29.

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: In this study, chitosan/alginate nanoparticles are prospected as a carrier for controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2).

Materials And Methods: The rhBMP-2-loaded chitosan/alginate nanoparticles (Cs/Alg/B NPs) were prepared using the ionic gelation (IG) method. The current research was conducted to optimize the effective factors for entrapping rhBMP-2 in Cs/Alg NPs using response surface methodology (RSM) and the Box-Behnken design (BBD). The variables were the Cs/Alg molecular weight (Mw) ratios (1-3), pH (4.8-5.5), stirring rates (900-1300 rpm) and the responses included size, ζ-potential, polydispersity index (PDI), loading efficacy (LE), cumulative release (CR), and morphological degradation time (MDE). Then, the morphological properties of optimum formulation were studied for post-characterization. In the next step, the MTT assay for the optimized run was done for 24 and 48 hours.

Results: The results revealed that the optimum conditions for the mentioned variables were stirring rate=1100 rpm, pH=5.15, and Cs/Alg Mw ratio=1.75 based on numerical optimization. It was shown that the average particle size and loading efficacy at optimum conditions were 253 nm and 67%, respectively. Other responses were as follows: CR=66%, ζ-potential=+35mV, PDI=0.5, and MDT=7 days.

Conclusion: The results have suggested that the statistical optimization of rhBMP-2 offers the possibility of preparing Cs/Alg/B NPs with a favorable size, controlled release characteristics, and high loading efficiency. It is expected that the acquired optimum conditions will be useful for efficient rhBMP-2 delivery.
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http://dx.doi.org/10.2147/IJN.S250630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606360PMC
November 2020

Development of a new electrochemical DNA biosensor based on Eu-doped NiO for determination of amsacrine as an anti-cancer drug: Electrochemical, spectroscopic and docking studies.

Anal Chim Acta 2020 Oct 12;1133:48-57. Epub 2020 Aug 12.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

The present research reported a new electrochemical biosensor based on ds-DNA/Eu doped NiO/CPE to detect amsacrine. Therefore, UV-Vis spectrophotometry, docking, and differential pulse voltammetry (DPV) have been used to study the interactions between amsacrine and dsDNA. Then, experimental parameters affected DNA immobilization and interactions between amsacrine and ds-DNA have been optimized. Afterwards, guanine oxidation peak current of ds-DNA has been chosen as a signal to analyze amsacrine in a concentration ranging between 0.1 and 100.0 μM and finally, limit of detection (LOD) of 0.05 μM has been calculated at optimal condition. Ultimately, it was found that the suggested biosensor is able to determine amsacrine in human serum and urine samples successfully.
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http://dx.doi.org/10.1016/j.aca.2020.07.071DOI Listing
October 2020

Nanofibrous Scaffolds Containing Hydroxyapatite and Microfluidic-Prepared Polyamidoamin/BMP-2 Plasmid Dendriplexes for Bone Tissue Engineering Applications.

Int J Nanomedicine 2020 21;15:2633-2646. Epub 2020 Apr 21.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering.

Methods: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated.

Results: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers.

Conclusion: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.
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http://dx.doi.org/10.2147/IJN.S244416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183354PMC
July 2020

In situ bone tissue engineering using gene delivery nanocomplexes.

Acta Biomater 2020 05 8;108:326-336. Epub 2020 Mar 8.

Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, USA; California NanoSystems Institute, University of California, Los Angeles, USA; Department of Bioengineering, University of California, Los Angeles, USA. Electronic address:

Gene delivery offers promising outcomes for functional recovery or regeneration of lost tissues at cellular and tissue levels. However, more efficient carriers are needed to safely and locally delivery of genetic materials. Herein, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexe (NC) platforms for bone tissue regeneration. pDNA encoding human bone morphogenesis protein-2 (BMP-2) was used as a gene of interest. Formation and fine-tuning of nanocomplexes (NCs) between pDNA and chitosan (CS) as carriers were performed using a micromixer platform. Flow characteristics were adjusted to tune mixing time and consequently size, zeta potential, and compactness of assembled NCs. Subsequently, NCs were immobilized on a nanofibrous Poly(ε-caprolactone) (PCL) scaffold functionalized with metalloprotease-sensitive peptide (MMP-sensitive). This construct can provide an environmental-sensitive and localized gene delivery platform. Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) was studied using chemical and biological assays. The presented results converge to indicate a great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine. STATEMENT OF SIGNIFICANCE: In this study, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexes (NCs) platforms for bone tissue regeneration. We used pDNA encoding human bone morphogenesis protein-2 (BMP-2) as the gene of interest. Using micromixer platform nanocomplexes (NCs) between pDNA and chitosan (CS) were fabricated and optimized. NCs were immobilized on a nanofibrous polycaprolactone scaffold functionalized with metalloprotease-sensitive peptide. In vitro and in vivo assays confirmed the osteogenic differentiation of mesenchymal stem cells (MSCs). The obtained data indicated great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine.
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http://dx.doi.org/10.1016/j.actbio.2020.03.008DOI Listing
May 2020

Multifunctional [email protected] as a theranostic agent for magnetic resonance imaging and targeting drug delivery: and study.

J Drug Target 2020 07 10;28(6):668-680. Epub 2020 Jan 10.

Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Owing to the importance of multifunctional theranostics as promising systems to overcome key problems of conventional cancer therapy, in this study a multifunctional metal-organic framework-based (MOF) theranostic system was prepared and applied as intelligent theranostic systems in cancer. Iron-based MOF, MIL-88B, in a multi-faceted shape was initially prepared. Curcumin (Cur) was then loaded into the pores of MIL and folic acid-chitosan conjugate (FC) was finally coated on the surface of the carrier to accomplish cancer-specific targeting properties. MTT assay revealed perfect cytocompatibility of the system and selective toxicity against cancerous cells. MRI images showed high tumour uptake for [email protected] and high T-T contrast effect. The growth inhibiting efficiencies of [email protected] on M109 tumour bearing Balb/C mice without reducing their body weight showed maximum tumour eradication with no significant toxicities. Due to the outstanding features of the system achieved from and studies, we believe that this study will provide a novel approach for developing targeted theranostic agents in cancer diagnosis and treatment.
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http://dx.doi.org/10.1080/1061186X.2019.1710839DOI Listing
July 2020

Pharmaceutical implants: classification, limitations and therapeutic applications.

Pharm Dev Technol 2020 Jan 12;25(1):116-132. Epub 2019 Nov 12.

Pharmaceutics Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Controlled/sustained delivery systems have been developed rapidly which show the ability to overcome the obstacles of traditional delivery systems. Daily development of biomedical and biomaterial sciences has brought more attention to the implantable delivery systems. As a result, these systems have found their position in the medical field since they were introduced. The advances in the polymeric science along with the other fields, make the production of a wide variety of implantable systems, possible. The influence of these systems in medical field could not be denied Here', the pharmaceutical applications which have been mostly focused on, are discussed. Since these systems have proven to be beneficial, researchers are trying to adjust their defects to the desired properties. Doing so, the path that implantable delivery systems have crossed so far should be studied, and that's the aim of this review. In the present report, the advantages of these systems in chemotherapeutic, contraceptive, neuropsychology, pain management, peptide delivery, ocular delivery, cardiovascular, orthopedic, and dental fields have been evaluated.
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http://dx.doi.org/10.1080/10837450.2019.1682607DOI Listing
January 2020

Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer's Disease: Behavioral and Biochemical Evidence.

J Alzheimers Dis 2019 ;69(3):671-686

Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-β (Aβ) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aβ-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g-1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aβ in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aβ-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.
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http://dx.doi.org/10.3233/JAD-190083DOI Listing
September 2020

[Corrigendum] Antiproliferative effects of imatinib mesylate on ZR‑75‑1 and MDA‑MB‑231 cell lines via PDGFR‑β, PDGF‑BB, c‑Kit and SCF expression.

Int J Mol Med 2019 05 4;43(5):2259. Epub 2019 Mar 4.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), 14176‑13151 Tehran, Iran.

An interested reader drew to our attention that the above study appeared to contain a high level of overlap with an article by the same authors published in the journal Drug Design, Development and Therapy [Kadivar A, Kamalidehghan B, Akbari Javar H, Karimi B, Sedghi R and Noordin MI: Antiproliferation effect of imatinib mesylate on MCF7, T‑47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR‑β, PDGF‑BB, c‑Kit and SCF genes. Drug Des Devel Ther 11: 469‑481, 2017]. Following an internal investigation and also in liaison with the authors, it was established that, although the studies were conducted along broadly similar lines, the papers contained entirely different data involving two different subsets of cell lines; the submission to Drug Des Devel Ther aimed to explore the effects of imatinib mesylate on three different groups, with each group being represented by a cell line, whereas the submission to Int J Mol Med explored the effectiveness of imatinib mesylate in breast cancer cell lines. In spite of this, considering the relatedness of the articles and the fact that the paper to Drug Des Devel Ther was submitted first and published while the Int J Mol Med paper was passing through the peer‑review process, the authors concede that they should have properly referenced their paper submitted to Drug Des Devel Ther in the Int J Mol Med paper. Note that the publishers of Drug Des Devel Ther, with whom we were liaising, agreed with the decision to issue a Corrigendum for this paper that acknowledges the article published in Drug Des Devel Ther. The authors regret their failure to acknowledge the related paper in this instance, and apologize to the readership for this oversight. [the original article was published in International Journal of Molecular Medicine 14: 414‑424, 2018; DOI: 10.3892/ijmm.2018.3590].
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http://dx.doi.org/10.3892/ijmm.2019.4119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443349PMC
May 2019

Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer's disease animal model by reducing Tau hyperphosphorylation.

Daru 2018 Dec 1;26(2):165-177. Epub 2018 Nov 1.

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Background: Nicotinamide is considered to be effective in halting the Alzheimer's disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful.

Method: Nicotinamide loaded solid lipid nanoparticles (SLN) were prepared and functionalized with polysorbate 80 (S80), phosphatidylserine (PS) or phosphatidic acid (PA). The acquired particles were characterized and evaluated in respect of their cytotoxicity, biodistribution, and in vivo effectiveness through the different routes of administration.

Results: The optimum sizes of 112 ± 1.6 nm, 124 ± 0.8 nm, and 137 ± 1.05 nm were acquired for S80-, PS-, and PA-functionalized SLNs, respectively. The in vitro cytotoxicity on SH-SY5Y cell line showed the safety of formulations except for S80-functionalized SLNs. Biodistribution study of SLNs has proved the benefits of functionalization in improving the brain delivery. The results of spatial and memory test, i.e. Morris water maze, and also histopathology and biochemical tests demonstrated the effectiveness of i.p. injection of PS -functionalized SLNs in improving the cognition, preserving the neuronal cells and reducing tau hyperphosphorylation in a rat model of Alzheimer's disease.

Conclusion: The acquired PS-functionalized SLN could be a potential brain delivery system. Loaded with nicotinamide, an HDAC inhibitor, it could ameliorate the cognition impairment of rats more effectively than the conventional administration of nicotinamide, i.e. oral, in the early stage of Alzheimer's disease. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s40199-018-0221-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279660PMC
December 2018

Brain Delivery of Curcumin Using Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Preparation, Optimization, and Pharmacokinetic Evaluation.

ACS Chem Neurosci 2019 01 24;10(1):728-739. Epub 2018 Oct 24.

Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Department of Pharmaceutical Nanotechnology, School of Pharmacy , Zanjan University of Medical Sciences , 45139-56184 Zanjan , Iran.

Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. In the current study, curcumin was encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the purpose of increasing brain accumulation. The preparation processes have been optimized using experimental design and multiobjective optimization methods. Entrapment efficiency of curcumin in SLNs and NLCs was found to be 82% ± 0.49 and 94% ± 0.74, respectively. The pharmacokinetic studies showed that the amount of curcumin available in the brain was significantly higher in curcumin-loaded NLCs (AUC = 505.76 ng/g h) compared to free curcumin (AUC = 0.00 ng/g h) and curcumin-loaded SLNs (AUC = 116.31 ng/g h) ( P < 0.005), after intravenous (IV) administration of 4 mg/kg dose of curcumin in rat. The results of differential scanning calorimetry and X-ray diffraction showed that curcumin has been dispersed as amorphous in the nanocarriers. Scanning electron microscopy images confirmed the nanoscale size and spherical shape of the nanoparticles. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging study indicated that preparation processes do not have any significant effect on the antioxidant activity of curcumin. The results of this study are promising for the use of curcumin-loaded NLCs in more studies and using curcumin in the treatment of CNS diseases.
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http://dx.doi.org/10.1021/acschemneuro.8b00510DOI Listing
January 2019

Tolerance induction by surface immobilization of Jagged-1 for immunoprotection of pancreatic islets.

Biomaterials 2018 11 10;182:191-201. Epub 2018 Aug 10.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. Electronic address:

Although transplantation of pancreatic islets is a promising approach for treatment of type 1 diabetes mellitus, the engraftment efficiency of these islets is limited by host immune responses. Extensive efforts have been made to immunoisolate these islets by introducing barriers on the islet surface. To date, these barriers have not successfully protected islets from attack by the immune system. In addition, the inevitable permeability of an islet capsule cannot prevent filtration by proinflammatory cytokines and islet self-antigens. Thus, we have developed a surface engineering approach for localized immonumodulation of the islet microenvironment. Jagged-1 (JAG-1), as a potent immunomodulatory factor, was immobilized on the islet surface by mediation of a double-layer of heterobifunctional poly (ethylene glycol) (PEG). Immobilization and functionality of JAG-1 on PEGylated islet surfaces were established. When co-cultured with splenocytes, the JAG-1 conjugated islets induced a significant increase in regulatory T cells and regulated the cytokine levels produced by immune cells. The results demonstrated that JAG-1 immobilization could improve immunoprotection of pancreatic islets by localized modulation of the immune milieu from an inflammatory to an anti-inflammatory state. We also evaluated the effects of surface modification of these islets by JAG-1 in a xenotransplantation model. The transplanted JAG-1/PEG/islets group showed a significantly reduced blood glucose levels compared with the control group of diabetic mice during the acute phase of the immune response to the transplanted islets. Our results demonstrated that surface modification has the potential to shift the immune system from an inflammatory to anti-inflammatory milieu and may offer a new prospective for immunoprotection of pancreatic islets.
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http://dx.doi.org/10.1016/j.biomaterials.2018.08.017DOI Listing
November 2018

Application of Response Surface Method for Preparation, Optimization, and Characterization of Nicotinamide Loaded Solid Lipid Nanoparticles.

Adv Pharm Bull 2018 Jun 19;8(2):245-256. Epub 2018 Jun 19.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Solid lipid nanoparticles (SLNs) have been proven to possess pharmaceutical advantages. They have the ability to deliver hydrophilic drugs through lipid membranes of the body. However, the loading of such drugs into SLNs is challenging. Hydrophilic nicotinamide, a histone deacetylase inhibitor, is used to establish SLNs with enhanced encapsulation efficiency by using statistical design. The possible effective parameters of these particles' characteristics were determined using pre-formulation studies and preliminary tests. Afterwards, the Response Surface Method (RSM) was utilized to optimize the preparation condition of SLNs. The effect of the amount of lipid, drug, surfactant, and the mixing apparatus were studied on particle size, zeta potential, and encapsulation efficiency of the obtained particles. The acquired particles were characterized in respect of their morphology, in vitro release profile, and cytotoxicity. According to this study, all the dependant variables could be fitted into quadratic models. Particles of 107 nm with zeta potential of about -40.9 and encapsulation efficiency of about 36% were obtained under optimized preparation conditions; i.e. with stearic acid to phospholipon® 90G ratio of 7.5 and nicotinamide to sodium taurocholate ratio of 14.74 using probe sonication. The validation test confirmed the model's suitability. The release profile demonstrated the controlled release profile following the initial burst release. Neither the nicotinamide nor the SLNs showed toxicity under the evaluated concentrations. The acquired results suggested the suitability of the model for designing the delivery system with a highly encapsulated water soluble drug for controlling its delivery.
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http://dx.doi.org/10.15171/apb.2018.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046421PMC
June 2018

Dexamethasone loaded multi-layer poly-l-lactic acid/pluronic P123 composite electrospun nanofiber scaffolds for bone tissue engineering and drug delivery.

Pharm Dev Technol 2019 Mar 29;24(3):338-347. Epub 2018 Jun 29.

c Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA-P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA-P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.
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http://dx.doi.org/10.1080/10837450.2018.1481429DOI Listing
March 2019

Evaluation of a novel biocompatible magnetic nanomedicine based on beta-cyclodextrin, loaded doxorubicin-curcumin for overcoming chemoresistance in breast cancer.

Artif Cells Nanomed Biotechnol 2018 24;46(sup2):207-216. Epub 2018 Apr 24.

f Department of Pharmaceutical Toxicology , Tehran University of Medical Sciences , Tehran , Iran.

Codelivery of chemo-sensitizers with chemotherapeutics using combo nanomedicine is a promising platform for overcoming chemoresistance in breast cancer. However, tumor accumulation of nano-carriers based on enhanced permeability and retention (EPR) effect is confounded by heterogeneity in tumor microenvironment. Adsorption of protein corona on surface of nanoparticle boost up clearance by reticulo-endothelial system. In this study, a surface functionalized magnetic nanocomposite (NC) for codelivery of doxorubicin (DOX) and curcumin (CUR) is developed. NCs were coated with hydroxyapatite and were also cross linked with β-cyclodextrin. NCs efficiently encapsulated DOX and CUR. Release of CUR and DOX were in a sustained pH-depended pattern. β-cyclodextrin functionalization reduced protein corona according sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. As shown by flowcytometric and confocal microscopy analyses, NCs internalized efficiently by human breast carcinoma cells MCF-7 and adriamycin resistant MCF-7 (MCF-7/adr) cells. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test demonstrated superior cytotoxicity of DOX-CUR loaded NCs. Anti-tumor efficacy analyses confirmed reduction in relative tumor volume size (RTV%) compared to control group. Western blot analyses demonstrated marginal CUR mediated P-glycoprotein (P-gp) down regulation. DOX-CUR loaded NCs efficiently accumulated into the tumor via external magnet guidance. Nevertheless, the increased tumor accumulation did not correlate with pharmacologic responses such as RTV% and significant superiority over free DOX was not observed.
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http://dx.doi.org/10.1080/21691401.2018.1453829DOI Listing
June 2019

Antiproliferative effects of imatinib mesylate on ZR‑75‑1 and MDA‑MB‑231 cell lines via PDGFR‑β, PDGF‑BB, c‑Kit and SCF expression.

Int J Mol Med 2018 Jul 27;42(1):414-424. Epub 2018 Mar 27.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), 14176‑13151 Tehran, Iran.

Imatinib mesylate is an anti‑neoplastic targeted chemotherapeutic agent, which can inhibit tyrosine kinase receptors, including BCR‑ABL, platelet‑derived growth factor receptors (PDGFRs) and c‑Kit. Cellular processes, including differentiation, proliferation and survival are regulated by these receptors. The present study aimed to evaluate the antiproliferative effects of imatinib mesylate, and its effects on apoptotic induction and cell cycle arrest in breast cancer cell lines. In addition, the study aimed to determine whether the effects of this drug were associated with the mRNA and protein expression levels of PDGFR‑β, c‑Kit, and their corresponding ligands PDGF‑BB and stem cell factor (SCF), which may potentially modulate cell survival and proliferation. To assess the antiproliferative effects of imatinib mesylate, an MTS assay was conducted following treatment of cells with 2‑10 µM imatinib mesylate for 96, 120 and 144 h; accordingly the half maximal inhibitory concentration of imatinib mesylate was calculated for each cell line. In addition, the proapoptotic effects and cytostatic activity of imatinib mesylate were investigated. To evaluate the expression of imatinib‑targeted genes, PDGFR‑β, c‑Kit, PDGF‑BB and SCF, under imatinib mesylate treatment, mRNA expression was detected using semi‑quantitative polymerase chain reaction and protein expression was detected by western blot analysis in ZR‑75‑1 and MDA‑MB‑231 breast carcinoma cell lines. Treatment with imatinib mesylate suppressed cell proliferation, which was accompanied by apoptotic induction and cell cycle arrest in the investigated cell lines. In addition, PDGFR‑β, PDGF‑BB, c‑Kit and SCF were expressed in both breast carcinoma cell lines; PDGFR‑β and c‑Kit, as imatinib targets, were downregulated in response to imatinib mesylate treatment. The present results revealed that at least two potential targets of imatinib mesylate were expressed in the two breast carcinoma cell lines studied. In conclusion, the antiproliferative, cytostatic and proapoptotic effects of imatinib mesylate may be the result of a reduction in the expression of c‑Kit and PDGFR tyrosine kinase receptors, thus resulting in suppression of the corresponding ligand PDGF‑BB. Therefore, imatinib mesylate may be considered a promising target therapy for the future treatment of breast cancer.
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http://dx.doi.org/10.3892/ijmm.2018.3590DOI Listing
July 2018

Fabrication of long-acting insulin formulation based on poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles: preparation, optimization, characterization, and in vitro evaluation.

Pharm Dev Technol 2019 Feb 26;24(2):176-188. Epub 2018 Mar 26.

a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.

The purpose of this research was the fabrication, statistical optimization, and in vitro characterization of insulin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (INS-PHBV-NPs). Nanopar-ticles were successfully developed by double emulsification solvent evaporation method. The NPs were characterized for particle size, entrapment efficiency (EE%), and polydispersity index (PDI). The NPs also were characterized by scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and circular dichroism (CD). The optimum conditions were found to be 1.6% polyvinyl alcohol (PVA), 0.9% of PHBV, and 15 mg/ml of insulin with the aid of the Box-Behnken experimental design results. The optimized NPs showed spherical shape with particle size of 250.21 ± 11.37 nm, PDI of 0.12 ± 0.01, and with EE% of 90.12 ± 2.10%. In vitro drug release pattern followed Korsmeyer-Peppas model and exhibited an initial burst release of 19% with extended drug release of 63.2% from optimized NPs within 27 d. In conclusion, these results suggest that INS-PHBV-NPs could be a promising candidate for designing an injectable sustained release formulation for insulin.
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http://dx.doi.org/10.1080/10837450.2018.1452936DOI Listing
February 2019

Development and characterization of electrosprayed nanoparticles for encapsulation of Curcumin.

J Biomed Mater Res A 2018 Jan 2;106(1):285-292. Epub 2017 Nov 2.

Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran, Iran.

Curcumin has been proven to be an effective herbal derived anti-inflammatory and antioxidant biocompatible agent. In this research, poly(lactic-co-glycolic acid) (PLGA) (as a biocompatible and generally recognized as safe (GRAS) polymer) nanoparticles containing Curcumin were electrosprayed from different polymeric solutions with different concentrations for the first time. Morphology of these nanoparticles in the absence/presence of Curcumin was evaluated by scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy analyses. Perfectly shaped nanoparticles with an average size of 300 and 320 nm were observed for neat and Curcumin-loaded PLGA, respectively. Curcumin-loaded electrosprayed nanoparticles showed a normal moderate initial burst and then a prolonged release period. Weibull, Peppas, and modified Korsmeyer-Peppas models were applied to study the kinetic and mechanism of Curcumin release from PLGA nanoparticles. Results showed high specific surface area and spherical geometry of the nanoparticles. Effectiveness of the electrospray method as a promising technique for preparing Curcumin-loaded nanoparticles was confirmed in this study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 285-292, 2018.
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http://dx.doi.org/10.1002/jbm.a.36233DOI Listing
January 2018

An improved surface for enhanced stem cell proliferation and osteogenic differentiation using electrospun composite PLLA/P123 scaffold.

Artif Cells Nanomed Biotechnol 2018 Sep 24;46(6):1274-1281. Epub 2017 Aug 24.

e Department of Pharmaceutical Biomaterials, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.

Poly-L-lactic acid (PLLA) nano fibrous scaffolds prepared by electrospinning technology have been used widely in tissue engineering applications. However, PLLA scaffolds are hydrophobic in nature, moreover the fibrous porous structure produced by electrospinning makes the scaffolds even more hydrophobic which generally limits cell attachment and proliferation. Polymer blending is one of the several efforts used so far to enhance hydrophilicity and recognized as an easy cost-effective approach for the manipulation physiochemical properties of polymeric biomaterials. Pluronic block copolymers containing hydrophilic poly(ethylene oxide) (PEO) blocks and hydrophobic poly(propylene oxide) (PPO) blocks are arranged in triblock structure: PEO-PPO-PEO. It is commonly used recently to blend hydrophobic polymers to enhance hydrophilicity for pharmaceutical and tissue engineering applications. In this study, novel pluronic P123 blend PLLA electrospun nanofibre scaffolds with improved hydrophilicity and biological properties were fabricated. The surface morphology and surface chemistry of the nanofibre scaffolds were characterized by scanning electron microscope (SEM) and FTIR analyses. Surface hydrophilicity and change in mechanical properties were studied. The ability of the scaffolds to support the attachment, and proliferation and differentiation of human adipose tissue derived MSCs, were evaluated generally. The fabricated scaffolds have completely improved, hydrophilicity, similar osteogenic differentiation potential with plasma-treated PLLA nanofibre scaffold, and hence P123 blend PLLA electrospun nanofibre scaffolds are a very good and cost effective choice as a scaffold for bone tissue engineering application.
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http://dx.doi.org/10.1080/21691401.2017.1367928DOI Listing
September 2018

Comparative analysis of essential oil composition of Iranian and Indian L. extracted using supercritical fluid extraction and solvent extraction.

Drug Des Devel Ther 2017 28;11:2221-2226. Epub 2017 Jul 28.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

The objective of this study was to compare the oil extraction yield and essential oil composition of Indian and Iranian L. extracted by using Supercritical Fluid Extraction (SFE) and solvent extraction methods. In this study, a gas chromatography equipped with a mass spectrophotometer detector was employed for qualitative analysis of the essential oil composition of Indian and Iranian L. The results indicated that the main fatty acid composition identified in the essential oils extracted by using SFE and solvent extraction were linoleic acid (22.4%-61.85%) and oleic acid (1.64%-18.97%). Thymoquinone (0.72%-21.03%) was found to be the major volatile compound in the extracted oil. It was observed that the oil extraction efficiency obtained from SFE was significantly (<0.05) higher than that achieved by the solvent extraction technique. The present study showed that SFE can be used as a more efficient technique for extraction of L. essential oil, which is composed of higher linoleic acid and thymoquinone contents compared to the essential oil obtained by the solvent extraction technique.
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http://dx.doi.org/10.2147/DDDT.S87251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546729PMC
April 2018

G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo.

J Biomed Mater Res A 2017 Oct 14;105(10):2830-2842. Epub 2017 Jul 14.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Sustained release of functional growth factors can be considered as a beneficial methodology for wound healing. In this study, recombinant human granulocyte colony-stimulating factor (G-CSF)-loaded chitosan nanoparticles were incorporated in Poly(ε-caprolactone) (PCL) nanofibers, followed by surface coating with collagen type I. Physical and mechanical properties of the PCL nanofibers containing G-CSF loaded chitosan nanoparticles PCL/NP(G-CSF) and in vivo performance for wound healing were investigated. G-CSF structural stability was evaluated through SDS_PAGE, reversed phase (RP) HPLC and size-exclusion chromatography, as well as circular dichroism. Nanofiber/nanoparticle composite scaffold was demonstrated to have appropriate mechanical properties as a wound dresser and a sustained release of functional G-CSF. The PCL/NP(G-CSF) scaffold showed a suitable proliferation and well-adherent morphology of stem cells. In vivo study and histopathological evaluation outcome revealed that skin regeneration was dramatically accelerated under PCL/NP(G-CSF) as compared with control groups. Superior fibroblast maturation, enhanced collagen deposition and minimum inflammatory cells were also the beneficial properties of PCL/NP(G-CSF) over the commercial dressing. The synergistic effect of extracellular matrix-mimicking nanofibrous membrane and G-CSF could develop a suitable supportive substrate in order to extensive utilization for the healing of skin wounds. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2830-2842, 2017.
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http://dx.doi.org/10.1002/jbm.a.36135DOI Listing
October 2017

Prolonged injectable formulation of Nafarelin using in situ gel combination delivery system.

Pharm Dev Technol 2018 Feb 5;23(2):132-144. Epub 2017 May 5.

a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Science , Tehran , Iran.

The principal purpose of the present study was to prepare and characterize a complex drug delivery system consisting of Nafarelin-poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) in combination with sodium alginate/poloxamer 407 in situ gel. Nafarelin-loaded PHBV NPs were prepared via double emulsion solvent evaporation technique. Box-Behnken Response Surface Methodology was utilized to optimize NPs. Mean particle size, polydispersity index (PDI), entrapment efficiency (EE), and drug loading (DL) of the optimized NPs were measured. Incorporation of Nafarelin within NPs was proven by differential scanning calorimetry (DSC). The combination delivery system (CDS) was prepared by adding Nafarelin-loaded PHBV NPs to sodium alginate/poloxamer 407 solution followed by physical mixing. Morphological properties of Nafarelin-loaded PHBV NPs and CDS were evaluated by SEM. Rheological properties were employed to investigate the effects of alginate concentration on sol-gel transition temperature. The release profile of Nafarelin from both PHBV NPs and CDS were individually assessed. The cumulative release percentage from CDS was significantly lower than Nafarelin released from PHBV NPs. Based on the favorable results in this study, the CDS consisting of sodium alginate/poloxamer 407 loaded with PHBV NPs could be a promising candidate for designing a long-lasting formulation of Nafarelin.
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http://dx.doi.org/10.1080/10837450.2017.1321662DOI Listing
February 2018

Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-β, PDGF-BB, c-Kit and SCF genes.

Drug Des Devel Ther 2017 21;11:469-481. Epub 2017 Feb 21.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2-10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer.
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http://dx.doi.org/10.2147/DDDT.S124102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327915PMC
May 2017

Nanotechnology for delivery of gemcitabine to treat pancreatic cancer.

Biomed Pharmacother 2017 Apr 28;88:635-643. Epub 2017 Jan 28.

Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.

Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now. However, its efficacy is unsatisfactory, mainly due to; its chemical instability and poor cellular uptake, resulting in an extremely short half-life and low bioavailability. To solve this drawbacks and increase the therapeutic outcome important progress has been achieved in the field of nanotechnology and offers a promising and effective alternative. This review mainly focus on the most commonly investigated nanoparticle (NP) delivery systems of Gem for PC treatment and the latest progresses achieved. Novel nanocarriers with better tumor targeting efficiencies and maximum treatment outcome to treat this deadly due are given much attention.
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http://dx.doi.org/10.1016/j.biopha.2017.01.071DOI Listing
April 2017

Efficient gene delivery to primary human retinal pigment epithelial cells: The innate and acquired properties of vectors.

Int J Pharm 2017 Feb 23;518(1-2):66-79. Epub 2016 Dec 23.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran; Medical Biomaterial Research Center (MBRC), Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran. Electronic address:

The purpose of this study is designing non-viral gene delivery vectors for transfection of the primary human retinal pigment epithelial cells (RPE). In the design process of gene delivery vectors, considering physicochemical properties of vectors alone does not seem to be enough since they interact with constituents of the surrounding environment and hence gain new characteristics. Moreover, due to these interactions, their cargo can be released untimely or undergo degradation before reaching to the target cells. Further, the characteristics of cells itself can also influence the transfection efficacy. For example, the non-dividing property of RPE cells can impede the transfection efficiency which in most studies was ignored by using immortal cell lines. In this study, vectors with different characteristics differing in mixing orders of pDNA, PEI polymer, and PLGA/PEI or PLGA nanoparticles were prepared and characterized. Then, their characteristics and efficacy in gene delivery to RPE cells in the presence of vitreous or fetal bovine serum (FBS) were evaluated. All formulations showed no cytotoxicity and were able to protect pDNA from premature release and degradation in extracellular media. Also, the adsorption of vitreous or serum proteins onto the surface of vectors changed their properties and hence cellular uptake and transfection efficacy.
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http://dx.doi.org/10.1016/j.ijpharm.2016.12.048DOI Listing
February 2017
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