Publications by authors named "Abbas Pardakhty"

55 Publications

Evaluation of potential anti-RNA-dependent RNA polymerase (RdRP) drugs against the newly emerged model of COVID-19 RdRP using computational methods.

Biophys Chem 2021 05 20;272:106564. Epub 2021 Feb 20.

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of medical sciences, Kerman, Iran. Electronic address:

Introduction: Despite all the efforts to treat COVID-19, no particular cure has been found for this virus. Since developing antiviral drugs is a time-consuming process, the most effective approach is to evaluate the approved and under investigation drugs using in silico methods. Among the different targets within the virus structure, as a vital component in the life cycle of coronaviruses, RNA-dependent RNA polymerase (RdRP) can be a critical target for antiviral drugs. The impact of the existence of RNA in the enzyme structure on the binding affinity of anti-RdRP drugs has not been investigated so far.

Methods: In this study, the potential anti-RdRP effects of a variety of drugs from two databases (Zinc database and DrugBank) were evaluated using molecular docking. For this purpose, the newly emerged model of COVID-19 (RdRP) post-translocated catalytic complex (PDB ID: 7BZF) that consists of RNA was chosen as the target.

Results: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These outcomes revealed that due to the ligand-protein interactions, the presence of RNA in this structure could remarkably affect the binding affinity of inhibitor compounds.

Conclusion: In silico approaches, such as molecular docking, could effectively address the problem of finding appropriate treatment for COVID-19. Our results showed that IDR and FNT have a significant affinity to the RdRP of SARS-CoV-2; therefore, these drugs are remarkable inhibitors of coronaviruses.
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http://dx.doi.org/10.1016/j.bpc.2021.106564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895701PMC
May 2021

[TBP]SO ionic liquid catalyst for 4MCR of pyridazinoindazole, indazolophthalazine and pyrazolophthalazine derivatives.

Mol Divers 2020 Nov 5. Epub 2020 Nov 5.

Pharmaceutics Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

Tetrabutyl phosphonium sulfate ([TBP]SO), as novel room-temperature ionic liquid (RTIL), was synthesized by a simple cost-effective method, characterized by H, C, P NMR and FT-IR spectrophotometry. The newly prepared catalyst was used as an efficient catalyst in some four multicomponent reactions (4MCRs) e. g., to synthesis pyridazino[1,2-a]indazole, indazolo[2,1-b]phthalazine and pyrazolo[1,2-b]phthalazine. This green method has several advantages such as short reaction time, using simple methods to prepare catalysts and products, easy operation and high efficiency of products. In addition, the catalyst can be easily recovered and reused several times with reduced average activity.
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http://dx.doi.org/10.1007/s11030-020-10153-8DOI Listing
November 2020

Niosomal virosome derived by vesicular stomatitis virus glycoprotein as a new gene carrier.

Biochem Biophys Res Commun 2021 01 31;534:980-987. Epub 2020 Oct 31.

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Virosomes as membranous vesicles with viral fusion protein in their membrane are versatile vehicles for cargo delivery. The vesicular stomatitis virus glycoprotein (VSV-G) is a common fusogenic protein used in virosome preparation. This glycoprotein has been used in liposomal systems so far, but in this study, we have tried to use the niosomal form instead of liposome for. Niosomes are vesicular systems composed of non-ionic surfactants. Niosomes were constructed by the thin-film hydration method. VSV-G gene in pMD2.G plasmid was expressed in the HEK293T cell line and then was reconstituted in the niosome bilayer. The formation of niosomal virosomes was confirmed with different methods such as SDS-PAGE gel, western blotting, and transmission electron microscopy (TEM). The efficiency of niosomal virosome was investigated with the pmCherry reporter gene. SDS-PAGE and western blotting proved the expression and successful insertion of protein into the bilayer. The TEM images showed the spike projection of VSV-G on the surface of niosomes. The transfection results showed high efficiency of niosomal virosomes as a novel carrier. This report has verified that niosome could be used as an efficient bilayer instead of liposome to construct virosomes.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.054DOI Listing
January 2021

In vivo gene delivery mediated by non-viral vectors for cancer therapy.

J Control Release 2020 09 4;325:249-275. Epub 2020 Jul 4.

Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey; Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul 34956, Turkey. Electronic address:

Gene therapy by expression constructs or down-regulation of certain genes has shown great potential for the treatment of various diseases. The wide clinical application of nucleic acid materials dependents on the development of biocompatible gene carriers. There are enormous various compounds widely investigated to be used as non-viral gene carriers including lipids, polymers, carbon materials, and inorganic structures. In this review, we will discuss the recent discoveries on non-viral gene delivery systems. We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Finally, we will delineate the state-of-the-art and promising perspective of in vivo gene editing using non-viral nano-vectors.
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http://dx.doi.org/10.1016/j.jconrel.2020.06.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334939PMC
September 2020

Nanotechnological Strategies for Osteoarthritis Diagnosis, Monitoring, Clinical Management, and Regenerative Medicine: Recent Advances and Future Opportunities.

Curr Rheumatol Rep 2020 04 4;22(4):12. Epub 2020 Apr 4.

Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Santariskiu 5, LT-08406, Vilnius, Lithuania.

Purpose Of Review: In this review article, we discuss the potential for employing nanotechnological strategies for the diagnosis, monitoring, and clinical management of osteoarthritis (OA) and explore how nanotechnology is being integrated rapidly into regenerative medicine for OA and related osteoarticular disorders.

Recent Findings: We review recent advances in this rapidly emerging field and discuss future opportunities for innovations in enhanced diagnosis, prognosis, and treatment of OA and other osteoarticular disorders, the smart delivery of drugs and biological agents, and the development of biomimetic regenerative platforms to support cell and gene therapies for arresting OA and promoting cartilage and bone repair. Nanotubes, magnetic nanoparticles, and other nanotechnology-based drug and gene delivery systems may be used for targeting molecular pathways and pathogenic mechanisms involved in OA development. Nanocomposites are also being explored as potential tools for promoting cartilage repair. Nanotechnology platforms may be combined with cell, gene, and biological therapies for the development of a new generation of future OA therapeutics. Graphical Abstract.
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http://dx.doi.org/10.1007/s11926-020-0884-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128005PMC
April 2020

Introducing new and effective catalysts for the synthesis of pyridazino[1,2-]indazole, indazolo[2,1-]phthalazine and pyrazolo[1,2-]phthalazine derivatives.

MethodsX 2020 20;7:100823. Epub 2020 Feb 20.

Pharmaceutics Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

In this study, a new and effective catalyst for the synthesis of pyridazino[1,2-]indazole, indazolo[2,1-]phthalazine and pyrazolo[1,2-]phthalazine derivatives was introduced. Triethanolammonium acetate ([TEAH][OAc]) accelerates the reaction in a one-pot and four-component condensation of aldehydes, hydrazine hydrate, succinic/phthalic anhydride, and 1,3-dicarbonyl compounds. The yield of the products is high, and the reaction conditions are mild and solvent-free. Furthermore, the model reaction was conducted in the presence of triethanolammonium sulphate ([TEAH][HSO] and triethanolammonium formate ([TEAH][HCOO]) under various conditions. In addition, the catalyst is recyclable, therefore, it can be reused several times. The structure of the obtained products was confirmed by comparing the M.P., IR, and H NMR. Advantages of this technique are as following:•Synthesis of novel, green, and one-pot and four-component condensation (4CC) under solvent-free conditions at room temperature.•The catalytic reaction is performed under mild and environmentally friendly conditions in short reaction times and excellent yields.•The catalyst is easily recycled and exhibits good chemical and structural stability.
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http://dx.doi.org/10.1016/j.mex.2020.100823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078373PMC
February 2020

Carbon dots as versatile nanoarchitectures for the treatment of neurological disorders and their theranostic applications: A review.

Adv Colloid Interface Sci 2020 Apr 19;278:102123. Epub 2020 Feb 19.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

The development of novel methods plays a fundamental role in early diagnosis and controlling of neurological disorders (NDs). Blood-brain barrier (BBB) is the most challenging barrier for the development of neuro drug delivery systems due to its inhibiting ability to enter drugs and agents into central nervous system (CNS). Carbon dots (CDs) have shown to be very promising and outstanding agents for various biomedical applications (bio imaging studies, treatment of NDs and brain tumors). They exhibit remarkable properties such as biocompatibility, small size (less than 10 nm, enabling penetration into BBB), tunable optical properties, photostability and simple synthetic procedures, allowing them to act as ideal candidates in various fields of science. Therefore, the objective of this review is to overview the recent studies on CDs for the development of neuro drug delivery systems to reach CNS via crossing of BBB. Primarily, this review briefly outlines the unique optical properties and toxicity of CDs. The development of novel neuro drug delivery systems for various neurological disorders using CDs as carriers is described. This review also covers the potential applications of CDs in brain tumors imaging and treatment of neurodegenerative diseases. Finally, the sensing applications and future prospects of CDs are summarized.
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http://dx.doi.org/10.1016/j.cis.2020.102123DOI Listing
April 2020

EMT signaling: potential contribution of CRISPR/Cas gene editing.

Cell Mol Life Sci 2020 Jul 1;77(14):2701-2722. Epub 2020 Feb 1.

Division of Pharmacy, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.

Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.
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http://dx.doi.org/10.1007/s00018-020-03449-3DOI Listing
July 2020

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics.

Biomedicines 2020 Jan 13;8(1). Epub 2020 Jan 13.

Enhanced Composites and Structures Center, School of Aerospace, Transport and Manufacturing, Cranfield University, Bedfordshire MK43 0AL, UK.

The blood-brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.
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http://dx.doi.org/10.3390/biomedicines8010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168063PMC
January 2020

Niosomal Benzoyl Peroxide and Clindamycin Lotion Versus Niosomal Clindamycin Lotion in Treatment of Acne Vulgaris: A Randomized Clinical Trial.

Adv Pharm Bull 2019 Oct 24;9(4):578-583. Epub 2019 Oct 24.

Department of Dermatology, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.

Combination of benzoyl peroxide (BPO) with topical antibiotics can lead to higher efficacy and less bacterial resistance, but it in turn increases adverse effects such as skin irritability and dryness. In this study, the efficacy of combination therapy of niosomal BPO 1% and clindamycin (CL) 1% is compared with niosomal CL in acne vulgaris. This is a double-blind clinical trial study on 100 patients with acne vulgaris in Afzalipour hospital in Kerman. Patients were randomly divided into 2 groups (case and control). The case group received niosomal combination of BPO 1% and CL 1%.The control group received niosomal CL1%. The efficacy of treatment protocols was evaluated in 2nd, 4th, 8th and 12th weeks of treatment by counting lesions (severity and grading acne lesions) and quality of life (QoL). Furthermore, side effect were evaluated at each treatment visits. The reduction in mean percentage of acne lesions in case group (treated with BPO 1% and CL1%) (64.21%) was higher than control group (treated with niosomal CL 1%) (59.04%), but the statistical difference was not significant. Sum of excellent and good results were found in 80% and 76.1% of case and control groups, respectively (P=0.377). Also adding BPO to the treatment formulation in case group did not increase adverse effects, as statistical difference between 2 groups was not significant. Combination of niosomal BPO 1% and CL 1% in treatment of acne vulgaris showed higher efficacy with no increase in adverse effects in comparison with niosomal CL 1%, but the statistical difference was not significant.
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http://dx.doi.org/10.15171/apb.2019.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912181PMC
October 2019

Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems.

Pharmacol Res 2020 01 17;151:104551. Epub 2019 Nov 17.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. Electronic address:

Topoisomerase enzymes have shown unique roles in replication and transcription. These enzymes which were initially found in Escherichia coli have attracted considerable attention as target molecules for cancer therapy. Nowadays, there are several topoisomerase inhibitors in the market to treat or at least control the progression of cancer. However, significant toxicity, low solubility and poor pharmacokinetic properties have limited their wide application and these characteristics need to be improved. Nano-delivery systems have provided an opportunity to modify the intrinsic properties of molecules and also to transfer the toxic agent to the target tissues. These delivery systems leads to the re-introduction of existing molecules present in the market as novel therapeutic agents with different physicochemical and pharmacokinetic properties. This review focusses on a variety of nano-delivery vehicles used for the improvement of pharmacological properties of topoisomerase inhibitors and thus enabling their potential application as novel drugs in the market.
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http://dx.doi.org/10.1016/j.phrs.2019.104551DOI Listing
January 2020

Nanoparticles Targeting STATs in Cancer Therapy.

Cells 2019 09 27;8(10). Epub 2019 Sep 27.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.

Over the past decades, an increase in the incidence rate of cancer has been witnessed. Although many efforts have been made to manage and treat this life threatening condition, it is still one of the leading causes of death worldwide. Therefore, scientists have attempted to target molecular signaling pathways involved in cancer initiation and metastasis. It has been shown that signal transducers and activator of transcription (STAT) contributes to the progression of cancer cells. This important signaling pathway is associated with a number of biological processes including cell cycle, differentiation, proliferation and apoptosis. It appears that dysregulation of the STAT signaling pathway promotes the migration, viability and malignancy of various tumor cells. Hence, there have been many attempts to target the STAT signaling pathway. However, it seems that currently applied therapeutics may not be able to effectively modulate the STAT signaling pathway and suffer from a variety of drawbacks such as low bioavailability and lack of specific tumor targeting. In the present review, we demonstrate how nanocarriers can be successfully applied for encapsulation of STAT modulators in cancer therapy.
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http://dx.doi.org/10.3390/cells8101158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829305PMC
September 2019

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems.

Biomolecules 2019 09 25;9(10). Epub 2019 Sep 25.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.
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http://dx.doi.org/10.3390/biom9100530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843293PMC
September 2019

Antileishmanial Activity of Niosomal Combination Forms of Tioxolone along with Benzoxonium Chloride against Leishmania tropica.

Korean J Parasitol 2019 Aug 31;57(4):359-368. Epub 2019 Aug 31.

Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 μg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.
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http://dx.doi.org/10.3347/kjp.2019.57.4.359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753291PMC
August 2019

Antileishmanial activity and immune modulatory effects of benzoxonium chloride and its entrapped forms in niosome on .

J Parasit Dis 2019 Sep 29;43(3):406-415. Epub 2019 Mar 29.

1Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Benzoxonium chloride is an anti-infective agent that is used as anti-septic drugs for disinfection of the mucus membrane, skin surface and anti-bacterial, and it is also found to be effective against cutaneous leishmaniasis. The present study aims to evaluate the leishmanicidal activity of benzoxonium chloride and niosomal forms against stages. Benzoxonium chloride niosomes were prepared by the thin film hydration method and evaluated for morphology, particle size and release study and encapsulation efficiency. This study measured the cytotoxicity, leishmanicidal activity against promastigote and intra macrophage amastigote, apoptosis, and mRNA transcripts by quantitative real time PCR (qPCR) of free solution and niosomal-encapsulated benzoxonium chloride. Span/Tween 60 niosomal formulation of benzoxonium chloride showed superior physical stability and high encapsulation efficiency (96%) than the other forms. Release from the formulations showed that the Span/Tween 60 containing drug had a milder gradient so that 10% of the drug was not released after 4 h. The benzoxonium chloride and niosomal forms inhibited the in vitro growth of promastigote and amastigote forms of after 48 h of incubation and represented IC values of 90.7 ± 2.7 and 25.4 ± 0.6 μg/ mL, respectively. The rate of apoptosis in niosomal formulations was approximately equal to the positive control (meglumine antimoniate) at the same concentration. Also, an increase in the concentration of this drug reduced the expression of IL-10, but increased the expression of IL-12. The niosomal formulations provided improved anti-leishmanial activities of benzoxonium chloride and played an immunomodulatory role as the mode of action in the treatment of anthroponotic CL.
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http://dx.doi.org/10.1007/s12639-019-01105-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667517PMC
September 2019

Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques.

Daru 2019 Dec 17;27(2):533-539. Epub 2019 Jul 17.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Background: Exosomes are natural nanoparticles that are involved in intercellular communication via transferring molecular information between cells. Recently, exosomes have been considered for exploitation as novel drug delivery systems due to their specific properties for carrying specific molecules and surface proteins.

Methods: In this study, U-87 cell derived exosomes have been investigated for delivery of a potent chemotherapeutic agent, paclitaxel (PTX). Two methods of loading were utilized to incorporate PTX in exosomes and the exosomes pharmaceutical and cytotoxic characterizations were determined.

Results: The drug loaded and empty exosomes were found to have particle size of 50-100 nm and zeta potential of ≈ - 20 mV. Loading capacity of 7.4 ng and 9.2 ng PTX into 1 μg of exosome total protein were also measured for incubation and sonication methods, respectively. Incorporation of PTX into exosomes significantly increased its cytotoxicity against U-87 cell line (59.92% cell viability) while it was found that the empty exosomes exhibited cell viability of 91.98%.

Conclusions: Loading method could affect the loading capacity of exosomes and their encapsulated chemotherapeutic molecule showed higher cytotoxicity into exosomes. These results promise exosomes as appropriate drug delivery system for glioblastoma multiform (GBM) treatment.
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http://dx.doi.org/10.1007/s40199-019-00280-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895332PMC
December 2019

The prevalence and predictors of using herbal medicines among Iranian cancer patients.

Complement Ther Clin Pract 2019 May 13;35:368-373. Epub 2019 Mar 13.

HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.

Background: and Purpose: Using of herbal medicines is common for cancer treatment. The aim of this study was to determine the prevalence, reasons, and predicting factors for the use of herbal medicines by Iranian cancer patients.

Materials And Methods: We conducted this cross-sectional study on 315 cancer patients through face-to-face interview in Kerman, Southeast of Iran, 2017.

Results: In total, 267 (84.1%) patients used at least one herbal medicine during chemotherapy courses, while only 42 (16.1%) patients discussed the use of herbal medicines with physicians. Living in urban regions (OR, 2.56; 95% CI, 1.30-5.05; P<0.0001) and the experience of constipation and diarrhea (OR, 2.11; 95% CI, 1.09-4.05; P = 0.02) were determined as some predicting factors for the use of herbal medicines.

Conclusion: Our findings indicate that as herbal medicines are common among cancer patients and their use is often overlooked, physicians should pay particular attention to herbal medicines during chemotherapy.
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http://dx.doi.org/10.1016/j.ctcp.2019.03.009DOI Listing
May 2019

Preparation of polyacrylamide/polylactic acid co-assembled core/shell nanofibers as designed beads for dapsone in vitro efficient delivery.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):917-926

a Pharmaceutics Research Center, Institute of Neuropharmacology , Kerman University of Medical Sciences , Kerman , Iran.

The main aim of this study is to synthesize and prepare polyacrylamide (PAM)/polylactic acid (PLA) co-assembled core/shell nanofibers in order to investigate an effective dapsone-loaded capability and dapsone-release in the aqueous medium. Dapsone (4,4-diamino-diphenyl sulfone) has high permeability and low solubility in water. In vitro release testing indicates that maximum incorporation of the dapsone nanoemulsions into core/shell nanofibrous structures were 77.71 after 400 min. Products were characterized with X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-Gravimetric Analysis (TGA), Dynamic light scattering (DLS) analysis, Contact Angle Measurement (CAM) and nitrogen adsorption [i.e. Brunauer-Emmett-Teller (BET) Surface Area Analysis] techniques. The porosimetric measurements of the nanofibers structures showed that high porosity diameter, adsorption cross-section area, pore volumes and dead volume were obtained as 0.162 nm, 0.1005 cmg and 15.693 cm, respectively. TGA curve of the core/shell nanofibrous structures shows thermal stability between 240 °C and 260 °C.
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http://dx.doi.org/10.1080/21691401.2019.1577881DOI Listing
December 2019

Shedding light on gene therapy: Carbon dots for the minimally invasive image-guided delivery of plasmids and noncoding RNAs - A review.

J Adv Res 2019 Jul 18;18:81-93. Epub 2019 Jan 18.

Neuroscience Research Center, Institute of Neuropharmacology, and Department of Toxicology & Pharmacology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Recently, carbon dots (CDs) have attracted great attention due to their superior properties, such as biocompatibility, fluorescence, high quantum yield, and uniform distribution. These characteristics make CDs interesting for bioimaging, therapeutic delivery, optogenetics, and theranostics. Photoluminescence (PL) properties enable CDs to act as imaging-trackable gene nanocarriers, while cationic CDs with high transfection efficiency have been applied for plasmid DNA and siRNA delivery. In this review, we have highlighted the precursors, structure and properties of positively charged CDs to demonstrate the various applications of these materials for nucleic acid delivery. Additionally, the potential of CDs as trackable gene delivery systems has been discussed. Although there are several reports on cellular and animal approaches to investigating the potential clinical applications of these nanomaterials, further systematic multidisciplinary approaches are required to examine the pharmacokinetic and biodistribution patterns of CDs for potential clinical applications.
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http://dx.doi.org/10.1016/j.jare.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383136PMC
July 2019

Novel CaO/polylactic acid nanoscaffold as dental resin nanocomposites and the investigation of physicochemical properties.

Luminescence 2019 May 27;34(3):360-367. Epub 2019 Feb 27.

Oral and Dental Disease Research Center, Kerman University of Medical Sciences, Kerman, Iran.

In this study, for the first time, calcium oxide (CaO)/polylactic acid nanoscaffolds were synthesized by co-precipitation assistant reverse micelles method. The physical and chemical (physicochemical) properties of the structures as dental resin composites were also studied. Nanocomposite materials as primary and basic dental compounds can be conveniently applied as dental filling materials with a high esthetic quality. In this research nanoscaffolds act as a bed for nanoparticles and improve the mechanical and chemical (mechanochemical) properties, CaO nanoparticles were loading in polylactic acid nanoscaffold as a bioactivity polymer for usage in the dental resin composites. Mechanical properties of the dental resin composite containing CaO/polylactic acid nanoscaffold were calculated: the flexural strength (137.2 MPa), modulus (12.9GPa) and compressive strength (344.2 MPa). Potential of the basic nanoparticle and the products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-visible) and atomic force microscopy (AFM) showed the size of the optimized nanostructures was about 85 to 120 nm. According to TGA results of polylactic acid nanofibers with thermal stability below 300°C these high thermal stability materials can be used as dental resin composites.
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http://dx.doi.org/10.1002/bio.3617DOI Listing
May 2019

Evaluation of the efficacy of intralesional Glucantime plus niosomal zinc sulphate in comparison with intralesional Glucantime plus cryotherapy in the treatment of acute cutaneous leishmaniasis, a randomized clinical trial.

J Parasit Dis 2018 Dec 13;42(4):616-620. Epub 2018 Oct 13.

1Leishmaniasis Research Center, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.

Current treatment modalities in cutaneous leishmaniasis have low efficacy and high toxicity as well as high rate of resistance to treatment. In this study, for the first time we decided to evaluate efficacy of intralesional Glucantime plus niosomal zinc sulphate in comparison with intralesional Glucantime plus cryotherapy in the treatment of acute cutaneous leishmaniasis. This is a case-control study on 64 patients with cutaneous leishmaniasis in Kerman-Iran. Patients were categorized in 2 groups A and B whom were treated with weekly intralesional meglumine antimonite plus twice daily niosomal topical zinc sulphate versus weekly intralesional Glucantime plus every other week cryotherapy, respectively. We assessed the efficacy of treatment modalities (as partial and complete response) and their adverse effects by measuring size of the lesions every 2 weeks up to maximum of 12 weeks and 3 months after the end of the treatment. Partial response rate was 16.6% and 12.9% in group A and B, respectively ( = 0.784). Complete response rate was 73.3% and 80.6% in group A and B, respectively ( = 0.784). Complete response rate was achieved in 4.73 ± 0.29 weeks and 4.69 ± 0.28 weeks in group A and B, respectively ( = 0.925). Partial response rate was achieved in 2.92 ± 0.23 weeks and 2.65 ± 0.18 weeks, respectively ( = 0.365). Combination of niosomal zinc sulphate with intralesional Glucantime has equal efficacy versus combination of cryotherapy plus intralesional Glucantime in the treatment of acute cutaneous leishmaniasis. So, it can be used in cases that have resistance to first-line treatments.
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http://dx.doi.org/10.1007/s12639-018-1044-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261150PMC
December 2018

In silico and in vitro study of magnetic niosomes for gene delivery: The effect of ergosterol and cholesterol.

Mater Sci Eng C Mater Biol Appl 2019 Jan 8;94:234-246. Epub 2018 Sep 8.

Department of Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

A low transfection efficiency and failure to deliver therapeutic genes to target organs limit the use of vesicular systems in gene therapy. In this study, magnetic niosomes were used to improve transfection efficiency and overcome limitations. In this light, Tween 60 and Span 60 molecules were employed as the bilayer component and ergosterol and/or cholesterol as membrane-stabilizing agents. We studied the structural and dynamical properties of cholesterol-containing niosomes (ST60/Chol) and ergosterol-containing vesicles (ST60/Ergo) using the molecular dynamics (MD) simulation technique. In in vitro experiments, the protamine-condensed DNA along with magnetic nanoparticles were prepared and incorporated into the niosome to form magnetic niosome-entrapped protamine-condensed DNA (M-NPD). The MD simulation comparison of two bilayers showed that the ST60/Ergo vesicles have better properties for gene delivery. Our in vitro results confirmed the in silico results and revealed that Ergo-niosomes have smaller size, better polydispersity, and slower release of plasmid than Chol-niosome. Moreover, M-NPD-Ergo showed higher cellular uptake and gene expresssion in HEK-293T cell line compared to M-NPD-Chol vesicles.
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http://dx.doi.org/10.1016/j.msec.2018.09.026DOI Listing
January 2019

A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels.

Med Hypotheses 2018 Dec 10;121:137-141. Epub 2018 Sep 10.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; School of Pharmacy and Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Thrombosis is a shared perpetrating event in the pathophysiology of several cardiovascular disorders such as ischemic stroke, venous thromboembolism, atherosclerosis, and myocardial infarction. Despite holding a wide range of ammunition in our arsenal to ameliorate such conditions, we are still facing with many stumbling blocks in the satisfactory pharmacotherapy of cardiovascular diseases among which the risk of hemorrhage and life threatening drug interactions can be highlighted. Our hypothesis focuses on mimicking the nature of platelet activation, to design a novel targeted delivery system based on the alterations of a physical parameter, the hemodynamic shear stress, to aim at the offending thrombi in an attempt to offer a noninvasive, rapid, and monitoring-free method that not only can prolong the circulation time of the cargo, but also deliver it locally and reduce both the undesirable adverse effects and drug interactions. Brij52 is our chosen candidate due to its unique non-spherical morphology after forming a niosomal vesicle. We surmised that thanks to its non-spherical shape, diverse shear rates may generate different shear stresses to its equators and axes which might result in the breakdown or at least distortion of niosomal structure under elevated shear stress. The vesicles have to be synthesized in the size of platelets or in the nano-sized scale. In order to prolong the time vesicles are circulating in the blood, PEGylation may help and to make such carriers highly selective to be only activated during pathophysiological clot formation, attachment of domain A1 von Willebrand factor can be of benefit to lead this proposed delivery system to the site of thrombus formation where shear rate exceeds those of 1000 s. There is now an emerging fast growing universal research on shear activated carriers, and the present theory is an endeavor to reach a successful treatment strategy to combat cardiovascular diseases based on the hypothesis that a non-spherical nano-carrier such as Brij 52 niosomal vesicle can be of paramount benefit to deliver current antithrombotic agents in a targeted and controlled manner in the presence of elevated shear stress of the obstructed blood vessels. With more radical advanced drug delivery systems being developed and new strategies being pursued, there will be more options in our arsenal to represent a promising avenue for achieving preventive, well-tolerated, and intelligent drug carriers to circumvent the drawbacks of antithrombotic pharmacotherapy.
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http://dx.doi.org/10.1016/j.mehy.2018.09.022DOI Listing
December 2018

Efficient drug delivery of β-estradiol encapsulated in Zn-metal-organic framework nanostructures by microwave-assisted coprecipitation method.

Drug Des Devel Ther 2018 28;12:2635-2643. Epub 2018 Aug 28.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran,

Metal-organic frameworks (MOFs) are structures made up of inorganic nodes, which can be either single ions or clusters of ions and organic linkers. This study reports on a novel processing route for producing β-estradiol encapsulated in Zn-MOF nanocomposites by microwave-assisted coprecipitation as a facile and fast method. Zn-MOF nanocomposites were synthesized with the aid of Zn(OAc)⋅2HO and 2,6-pyridine dicarboxylic acid ammonium as an organic ligand. Furthermore, we studied encapsulated β-estradiol which is one of the most important classes of estrogenic compounds that are used in the treatment of prostate cancer and breast cancer. The effects of β-estradiol concentration and microwave irradiation on the morphology, particle size, distribution, and in vitro photoluminescence spectroscopy experiments of β-estradiol entrapped in Zn-MOF nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and Brunauer-Emmett-Teller spectroscopy. These nanostructures can be a good option for thawing hydrophilic and hydrophobic drugs over time. Zn-MOF nanocomposites with high porosity, total pore volume (0.04665 cmg), and nanostructures have provided the platform to load β-estradiol such as low soluble drugs. Maximum of drug release was about 82% at pH 8.9 after 8 h.
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http://dx.doi.org/10.2147/DDDT.S173324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118239PMC
December 2018

Proliferation and In Vitro Wound Healing Effects of the Microniosomes Containing Narcissus tazetta L. Bulb Extract on Primary Human Fibroblasts (HDFs).

Daru 2018 Sep 12. Epub 2018 Sep 12.

Physiology Research Center; Neuropharmacology Institute, Kerman University of Medical Sciences, Ibne cina street, Kerman, Iran.

Purpose: In Traditional Persian Medicine (TPM), different natural treatments have been suggested for skin damages such as Narcissus tazetta L. bulb application. New drug delivery systems such as niosomes have shown considerable increase transdermal drug delivery through stratum corneum, the main barrier against substances transport into skin. The aim of this study is preparation of niosomal formulations from N. tazetta bulb extract and evaluation of its in vitro wound healing effect.

Materials And Methods: Non-ionic surfactant vesicles (NSVs or niosomes) were prepared by film hydration method from percolated extract of N. tazetta bulb. A number of 12 niosomal formulations (F1-F12) were prepared using different proportions of Span 60/Tween 60/cholesterol and 80% methanol-dissolved/aqueous PEN (percolation extract of N. tazetta) (30 and 50 mg/ml). Their morphology, particle size, physical and chemical stability and encapsulation efficiency was studied. In vitro wound healing effect of various concentrations of the best PEN niosomal formulation (F9) was evaluated in comparison to PEN on human dermal fibroblasts (HDFs).

Results: Increasing the aqueous/methanolic PEN concentration from 3 to 5% resulted size reduction of NSVs with statistically significant difference (p < 0.05). F9 showed the most physicochemical stability and was chosen for in vitro wound healing effect. This formulation exhibited significantly effects (p < 0.05) on cell proliferation in HDF cells at 1.562 and 3.125 μg/ml compared with the untreated cells using neutral red assay.

Conclusion: Formulation of PEN in niosome carrier significantly decreased the gap width on human dermal fibroblasts. Graphical abstract Schematic processes of proliferation effect of narcisus tazetta bulb on fibroblast cells.
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http://dx.doi.org/10.1007/s40199-018-0211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154482PMC
September 2018

Phytoniosome: a Novel Drug Delivery for Myrtle Extract.

Iran J Pharm Res 2018 ;17(3):804-817

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Traditionally, (myrtle) has been used for treatment of several kinds of disorders. However, there are some factors, namely, low solubility and permeability, which restrict use of myrtle extract (ME) in medical applications. Regarding these limitations, the aim of the present study was to develop a new niosomal formulation to enhance ME stability and permeability. Briefly, several niosomal formulations were prepared by non-ionic surfactants and cholesterol with different molar ratios. Afterward, size, entrapment efficiency (EE%), release and stability of niosomal myrtle extract (nME) were investigated. The effect of ME and nME on viability of 3T3 cells was evaluated using MTT assay. Antibacterial activity of ME and nME was also assessed against , , . Sizes of niosomes were 5.3 ± 0.3 to 15.9 ± 2.2 µm with 4.1 ± 0.3 to 26.9 ± 1.7 mV zeta potential. The EE% of niosomes was varied from 45.4% to 93.4%. An release study on F5 formulation (Span60: Tween60: cholesterol (3:3:4 molar ratio)) revealed that about 36.9%, 38.5% and 26.7% of phytoconstituents were released within 12 h from acetate cellulose membrane, 0.45 µm, regenerated cellulose membrane, 0.45 µm, and cellophane dialysis sack, 12000 Da, respectively. F5 formulation significantly showed lower toxicity on cells. It had higher antibacterial activity that has been shown by lower MICs and higher zone of inhibition compared to ME. Overall, F5 formulation in the presence of 4% ME produced stable multi lamellar vesicles with optimal release and EE%. This formulation also exhibited better antibacterial activity than ME.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094422PMC
January 2018

Development, physicochemical characterization, and antimicrobial evaluation of niosomal myrtle essential oil.

Res Pharm Sci 2018 Jun;13(3):250-261

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, I.R. Iran.

(myrtle) is well known for its therapeutic effects pertaining to the major secondary metabolites including essential oils (EOs). EOs are composed of volatile compounds and simply evaporate or decompose leading to their instability. Preparation of EOs niosomal formulation may be a promising approach to deal with these obstacles. Niosomal formulations of myrtle essential oil (nMEO) were provided using non-ionic surfactants and cholesterol (Chol). In the next steps, vesicle size, zeta potential, percentage of entrapment efficiency (EE%) and physical stability of nMEO were investigated. Finally, the effect of myrtle essential oil (MEO) and nMEO on microbial growth inhibition were assessed. Values for nMEO size and zeta potential ranged from 6.17 ± 0.32 to 7.24 ± 0.61 (μm) and -20.41 ± 0.17 to -31.75 ± 0.45 (mV), respectively. Higher degrees of EE% were obtained by F6 formulation (Span/Tween 60:Chol (50:50 molar ratio)). Moreover, niosomes have been reported to be stable at 4 °C during a three-month time period. It was revealed that nMEO F6 formulation inhibited growth of , , and at concentrations lower than that of MEO. Overall, it was found that stable multilamellar vesicles were formed in the presence of 0.5% MEO and F6 formulation. This formulation also exhibited better antibacterial activity than MEO.
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http://dx.doi.org/10.4103/1735-5362.228955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921405PMC
June 2018

Niosomes, an alternative for liposomal delivery.

PLoS One 2018 12;13(4):e0194179. Epub 2018 Apr 12.

Department of Biochemistry, University of Groningen, Groningen, The Netherlands.

Niosomes are used in studies for drug delivery or gene transfer. However, their physical properties and features relative to liposomes are not well documented. To characterize and more rationally optimize niosome formulations, the properties of these vesicle systems are compared to those of liposomes composed of phosphatidylcholine and phosphatidylethanolamine lipids plus cholesterol. Niosomes are highly stable and only slightly more leaky than liposomes as assayed by calcein leakage; the permeability for ions (KCl) is higher than that of liposomes. Contrary to liposomes, the size of niosomes decreases substantially upon freezing in liquid nitrogen and subsequent thawing, as shown by cryo-EM and dynamic light scattering. The packing of niosomal membranes was determined by laurdan fluorescence and is slightly lower than that of liposomes. We did not succeed in the functional reconstitution of the L-arginine/L-ornithine antiporter ArcD2 in niosomes, which we attribute to the non-ionic nature of the surfactants. The antimicrobial peptides alamethicin and melittin act similarly on niosomes and liposomes composed of unsaturated components, whereas both niosomes and liposomes are unaffected when saturated amphiphiles are used. In conclusion, in terms of stability and permeability for drug-size molecules niosomes are comparable to liposomes and they may offer an excellent, inexpensive alternative for delivery purposes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194179PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896898PMC
July 2018

Comparison the Pain Relief of Amitriptyline Mouthwash with Benzydamine in Oral Mucositis.

J Dent (Shiraz) 2018 Mar;19(1):34-40

Specialist in Oral Medicine, Research Center for Prevention of Oral and Dental Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Statement Of The Problem: A significant proportion of patients undergoing chemotherapy or radiotherapy suffer from mucositis. The first symptom of oral mucositis is pain. Severe pain, burning sensation, and discomfort in the oral cavity make it difficult to continue treatment and even continue living in these patients.

Purpose: The aim of this study was to evaluate and compare the effect of amitriptyline mouthwash (in two forms of simple and niosomal) as a local anesthetic agent with benzydamine HCl mouthwash in oral mucositis after radiotherapy or chemotherapy.

Materials And Method: This double-blind study was performed on 60 patients with oral mucositis caused by radiotherapy and chemotherapy. The severity of mucositis was determined based on patient judgment; then dental examination was performed and recorded in a checklist. Three groups were assigned based on using either benzydamine HCL, amitriptyline, or niosomal form of amitriptyline. Pain and burning sensation were evaluated with VAS at different time intervals: before use and one, five, ten, and thirty minutes and one hour after using mouthwash. T-test was used to compare the intensity of pain between the two groups. ANOVA and Tukey test were used to compare the intensity of pain between groups.

Results: Statistical analyses showed the maximum reduction in pain intensity at two different time intervals (= 0.04). Ten minutes after the use of niosomal form of amitriptyline, a 95% decrease in pain was observed. A 99% reduction in pain occurred after the use of simple form of amitriptyline (= 0.04).

Conclusion: Use of amitriptyline mouthwash had local anesthetic effects in oral mucositis without systemic side effects. Decrease in the severity of pain with the use of amitriptyline mouthwash was more than that of benzydamine HCL mouthwash.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817341PMC
March 2018

Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine.

Artif Cells Nanomed Biotechnol 2018 Dec 28;46(8):1781-1791. Epub 2017 Oct 28.

b Department of Biochemistry, School of Medicine , Kerman University of Medical Sciences , Kerman , Iran.

Non-viral gene delivery methods are considered due to safety and simplicity in human gene therapy. Since the use of cationic peptide and niosome represent a promising approach for gene delivery purposes we used recombinant fusion protein and cationic niosome as a gene carrier. A multi-domain fusion protein including nuclear localization motif (NLS) and two DNA-binding (Mu) domains, namely NLS-Mu-Mu (NMM) has been designed, cloned and expressed in E. coli DE3 strain. Afterward, the interested protein was purified by affinity chromatography. Binary vectors based on protein/DNA and ternary vectors based on protein/DNA/niosome were prepared. Protamine was used as a control. DNA condensing properties of NMM and protamine were evaluated by various experiments. Furthermore, we examined cytotoxicity, hemolysis and transfection potential of the binary and ternary complexes in HEK293T and MCF-7 cell lines. Protamine and Lipofectamine™2000 were used as positive controls, correspondingly. The recombinant NMM was expressed and purified successfully and DNA was condensed efficiently at charge ratios that were not harmful to cells. Peptidoplexes showed transfection efficiency (TE) but ternary complexes had higher TE. Additionally, NMM ternary complex was more efficient compared to protamine ternary vectors. Our results showed that niosomal ternary vector of NMM is a promising non-viral gene carrier to achieve an effective and safe carrier system for gene therapy.
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http://dx.doi.org/10.1080/21691401.2017.1392316DOI Listing
December 2018