Publications by authors named "Imran Tariq"

23 Publications

  • Page 1 of 1

Enhanced Efficacy and Drug Delivery with Lipid Coated Mesoporous Silica Nanoparticles in Cancer Therapy.

Eur J Pharm Biopharm 2021 May 4. Epub 2021 May 4.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany.

The exposure of cancer cells to subtherapeutic drug concentrations result in multi drug resistance (MDR). The uniqueness of mesoporous silica nanoparticles (MSNPs) with larger surface area for higher drug loading can solve the issue by delivering higher amounts of chemotherapeutics to the cancer cells. However premature drug release and lower biocompatibility remain challenging. Lipid coating of MSNPs at the same time, can enhance the stability and biocompatibility of nanocarriers. Furthermore, the lipid coating can reduce the systemic drug release and deliver higher amounts to the tumor site. Herein, lipid coated MSNPs were prepared by utilizing cationic liposomes and further investigations were made. Our studies have shown the higher entrapment of doxorubicin (Dox) to MSNPs due to availability of porous structure. Lipid coating could provide a barrier to sustain the release of drug along with reduced premature leakage. In addition, the biocompatibility and enhanced interaction of cationic liposomes to cell membranes resulted in better cellular uptake. Lipid coated silica nanoparticles have shown higher cellular toxicity as compared to non-lipid coated particles. The increase in cytotoxicity with time supports the hypothesis of sustained release of drug from lipid coated MSNPs. We propose the Lip-Dox-MSNPs as an effective approach to treat cancer by delivering and maintaining effective concentration of drugs to the tumor site without systemic side effects.
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http://dx.doi.org/10.1016/j.ejpb.2021.04.020DOI Listing
May 2021

Lipoparticles for Synergistic Chemo-Photodynamic Therapy to Ovarian Carcinoma Cells: In vitro and in vivo Assessments.

Int J Nanomedicine 2021 11;16:951-976. Epub 2021 Feb 11.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany.

Purpose: Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers.

Methods: For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice.

Results And Conclusion: The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.
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http://dx.doi.org/10.2147/IJN.S285950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884954PMC
March 2021

ADAM 8 as a novel target for doxorubicin delivery to TNBC cells using magnetic thermosensitive liposomes.

Eur J Pharm Biopharm 2021 Jan 16;158:390-400. Epub 2020 Dec 16.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany. Electronic address:

Metastatic breast cancer is one of the most common causes of cancer-related death in women worldwide. The transmembrane metalloprotease-disintegrin (ADAM8) protein is highly overexpressed in triple-negative breast cancer (TNBC) cells and potentiates tumor cell invasion and extracellular matrix remodeling. Exploiting the high expression levels of ADAM8 in TNBC cells by delivering anti-ADAM8 antibodies efficiently to the targeted site can be a promising strategy for therapy of TNBC. For instance, a targeted approach with the aid of ultra-high field magnetic resonance imaging (UHF-MRI) activatable thermosensitive liposomes (Lip) could specifically increase the intracellular accumulation of cytotoxic drugs. The surface of doxorubicin-loaded Lip was modified by covalent coupling of MAB1031 antibody (Lip) in order to target the overexpressed ADAM8 in ADAM8 positive MDA-MB-231 cells. Physicochemical characterization of these liposomes was performed using size, surface morphology and UHF-MRI imaging analysis. In vitro cell targeting was investigated by the washing and circulation method. Intracellular trafficking and lysosomal colocalization were assessed by fluorescence microscopy. Cell viability, biocompatibility and in-ovo CAM assays were performed to determine the effectiveness and safety profiles of liposome formulations. Our results show specific binding and induction of doxorubicin release after Lip treatment caused a higher cytotoxic effect at the cellular target site.
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http://dx.doi.org/10.1016/j.ejpb.2020.12.012DOI Listing
January 2021

Lipodendriplexes mediated enhanced gene delivery: a cellular to pre-clinical investigation.

Sci Rep 2020 12 8;10(1):21446. Epub 2020 Dec 8.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037, Marburg, Germany.

Clinical success of effective gene therapy is mainly hampered by the insufficiency of safe and efficient internalization of a transgene to the targeted cellular site. Therefore, the development of a safe and efficient nanocarrier system is one of the fundamental challenges to transfer the therapeutic genes to the diseased cells. Polyamidoamine (PAMAM) dendrimer has been used as an efficient non-viral gene vector (dendriplexes) but the toxicity and unusual biodistribution induced by the terminal amino groups (-NH) limit its in vivo applications. Hence, a state of the art lipid modification with PAMAM based gene carrier (lipodendriplexes) was planned to investigate theirs in vitro (2D and 3D cell culture) and in vivo behaviour. In vitro pDNA transfection, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, cellular protein contents, live/dead staining and apoptosis were studied in 2D cell culture of HEK-293 cells while GFP transfection, 3D cell viability and live/dead staining of spheroids were performed in its 3D cell culture. Acute toxicity studies including organ to body index ratio, hematological parameters, serum biochemistry, histopathological profiles and in vivo transgene expression were assessed in female BALB/c mice. The results suggested that, in comparison to dendriplexes the lipodendriplexes exhibited significant improvement of pDNA transfection (p < 0.001) with lower LDH release (p < 0.01) and ROS generation (p < 0.05). A substantially higher cellular protein content (p < 0.01) and cell viability were also observed in 2D culture. A strong GFP expression with an improved cell viability profile (p < 0.05) was indicated in lipodendriplexes treated 3D spheroids. In vivo archives showed the superiority of lipid-modified nanocarrier system, depicted a significant increase in green fluorescent protein (GFP) expression in the lungs (p < 0.01), heart (p < 0.001), liver (p < 0.001) and kidneys (p < 0.001) with improved serum biochemistry and hematological profile as compared to unmodified dendriplexes. No tissue necrosis was evident in the animal groups treated with lipid-shielded molecules. Therefore, a non-covalent conjugation of lipids with PAMAM based carrier system could be considered as a promising approach for an efficient and biocompatible gene delivery system.
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http://dx.doi.org/10.1038/s41598-020-78123-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723038PMC
December 2020

Sensitivity of Papilloma Virus-Associated Cell Lines to Photodynamic Therapy with Curcumin-Loaded Liposomes.

Cancers (Basel) 2020 Nov 5;12(11). Epub 2020 Nov 5.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, 35033 Marburg, Germany.

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach used in the treatment of various medical conditions and cancerous diseases, involving light, a photosensitizing substance, and oxygen. Curcumin, a naturally occurring compound, carries antitumor activities and potentially could be exploited as a photosensitizer in PDT. Only little is known about liposomal-encapsulated curcumin that could help in increasing the efficacy, stability, and bioavailability of this compound. This study investigates the in vitro effects of curcumin-loaded liposomes in combination with PDT. Three papilloma virus-associated cell lines were treated with curcumin-loaded liposomes corresponding to a curcumin concentration of 0-100 µmol/L for 4 h followed by illumination at 457 nm (blue) for 45, 136, and 227 s at a fluence of 220.2 W/m (100 mA) corresponding to 1, 3 and 5 J·cm. After 24 h, the biological outcome of the treatment was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), SYTO9/PI (propidium iodide), Annexin V-FITC (fluorescein isothiocyanate)/PI, clonogenic survival, and scratch (wound closure) assays. Photoactivation of curcumin-loaded liposomes led to a significant reduction in colony formation and migratory abilities, as well as to an increase in tumor cell death. The results point to the combination of curcumin-loaded liposomes with PDT as a potentially useful tool for the treatment of papillomavirus-associated malignancies.
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http://dx.doi.org/10.3390/cancers12113278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694491PMC
November 2020

Potent Cytotoxicity of Four Cameroonian Plant Extracts on Different Cancer Cell Lines.

Pharmaceuticals (Basel) 2020 Oct 31;13(11). Epub 2020 Oct 31.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany.

In this study, the potential cytotoxicity of four plant extracts originated from Cameroon: (XA), (IC), (EG) and (DP) were examined in vitro. We tested the anti-proliferative activity of the methanolic extracts of these compounds using MTT assay on seven different human cancer cell lines: HeLa, MDA-MB-231, A549, HepG2, U-87, SK-OV-3 and HL60. Induction of cell death was assessed by cell cycle analysis, apoptosis was determined by Annexin V-FITC binding and caspase 3/7 activity. As well, changes in mitochondrial membrane potential (MMP) and cell migration were tested. The genetic toxicity, using the alkaline comet assay, was evaluated. The studied extracts inhibited the cell proliferation of all tested cancer cell lines with concentration dependent effect over time. All of these extracts mainly induced apoptosis of HeLa cells by the accumulation of hypodiploid cells in the sub-G0/G1 phase and increasing the activity of caspase 3/7, as well they showed potential MMP disturbance and expressed a marked inhibitory effect on cell migration. Assessment of probable genetic toxicity by these extracts revealed no or minimum incidence of genetic toxicity. Therefore, the studied plant extracts are exhibiting potent anticancer activity based upon marked induction of tumor-cell death.
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http://dx.doi.org/10.3390/ph13110357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693157PMC
October 2020

Downregulation of MDR 1 gene contributes to tyrosine kinase inhibitor induce apoptosis and reduction in tumor metastasis: A gravity to space investigation.

Int J Pharm 2020 Dec 18;591:119993. Epub 2020 Oct 18.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany. Electronic address:

P-glycoprotein (P-gp) associated multidrug resistance (MDR) represents a major failure in cancer treatment. The overexpression of P-gp is responsible for ATP-dependent efflux of drugs that decrease their intracellular accumulation. An effective downregulation of MDR1 gene using small interfering RNA (siRNA) is one of the safe and effective tools to overcome the P-gp triggered MDR. Therefore, the development of an efficient and non-toxic carrier system for siRNA delivery is a fundamental challenge for effective cancer treatment. Polyamidoamine (PAMAM) dendrimer has been used for efficient delivery of siRNA (dendriplexes) to the tumor cells but the associated toxicity problems render its use in biological applications. A non-covalent lipid modification (lipodendriplexes) is supposed to offer a promising strategy to overcome the demerits linked to the naked dendriplexes system. In the current study, we deliver siRNA, designed against MDR1 gene (si-MDR1), in colorectal carcinoma cells (Caco-2), having overexpression of P-gp, to check the role of MDR1 gene in tumor progression and multidrug resistance using two dimensional (2D) and three dimensional (3D) environment. Imatinib mesylate (IM), a P-gp substrate, was used as model drug. Our results revealed that the effective knockdown by lipodendriplexes system can significantly reduce the tumor cell migration in 2D (p < 0.001) and 3D (p < 0.001) cell cultures as compared to unmodified dendriplexes and si-Control groups. It was also observed that lipodendriplexes aided downregulation of MDR1 gene effectively, re-sensitized the Caco-2 cells for IM uptake and showed a significantly (p < 0.001) higher apoptosis. Our findings imply that our lipodendriplexes system has a great potential for siRNA delivery, however, further in vivo application using a suitable targeted system can play a major role for better cancer therapeutics.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119993DOI Listing
December 2020

Development and Characterization of Ultrasound Activated Lipopolyplexes for Enhanced Transfection by Low Frequency Ultrasound in In Vitro Tumor Model.

Macromol Biosci 2020 12 3;20(12):e2000173. Epub 2020 Sep 3.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert Koch Straße 4, Marburg, 35037, Germany.

This work focuses on the development of ultrasound contrast vesicles for ultrasound-mediated enhanced transfection of nucleic acids in the cancer cells and projects its application as a tool for diagnostic imaging. The ultrasound contrast vesicles are stable, anionic, nanoscaled vesicles with ultrasound contrast equivalent to the commercially available SonoVue. These anionic lipid vesicles establish electrostatic interaction with cationic polyplexes based on linear polyethylenimine (22kDa) forming lipopolyplexes with ultrasound contrast. The lipopolyplexes are characterized regarding shape, size, and zeta potential. When exposed to low frequency ultrasound, these carriers show elevated transfection efficiency and reduced cytotoxicity. The effect of post-transfection ultrasound on cellular uptake of lipopolyplexes is also evaluated. An analogous transfection is also observed in the tumor mimicking multicellular 3D spheroid culture of ovarian cancer cells. The emergence of tumor imaging and enhanced gene delivery by medical ultrasound, a noninvasive imaging modality, is considered paving the way for efficient theranostic gene therapy.
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http://dx.doi.org/10.1002/mabi.202000173DOI Listing
December 2020

First report of brown leaf spot of rice caused by Bipolaris zeicola in Pakistan.

Plant Dis 2020 Aug 17. Epub 2020 Aug 17.

University of Agriculture Faisalabad, 66724, Entomology, Faisalabad, Punjab, Pakistan;

Rice (Oryza sativa L.) is one of the highly consumed cereal grain crops in Pakistan. In September 2017, leaf samples of cultivar Basmati-385 showing brown to dark brown spots (5 to 9 mm in diameter) that were oval or cylindrical in shape with a chlorotic yellow halo and grayish tan centers were collected from fields near the University of Agriculture, Faisalabad (31.43633 N 73.05981 E). Average disease incidence was 69% in six rice fields that were sampled for diseased plants with visible symptoms. To isolate the pathogen, from 20 diseased leaves, 5 mm2 segments from the margins of lesions were cut, rinsed with sterile distilled water (SDW), surface disinfected by 70% ethanol and again rinsed with SDW. The samples were dried on sterilized filter paper discs, plated on potato dextrose agar (PDA) and incubated at 27°C for 5 to 7 days. Twelve isolates were sub-cultured and single-sporing was performed to obtain pure cultures. Fungal isolates with light to dark gray in color, thick or fluffy aerial mycelium, circular and smooth margins were obtained after 7 days of incubation. Conidia were 47-83 μm × 10-17 μm (n=100), with 4 to 10 distosepta, dark or olivaceous brown, straight or moderately curved, and the cells at the ends occasionally looked paler than those in the middle. Conidiophore of the fungus were simple, smooth, cylindrical, septate, and straight to flexuous. These characteristics resembled those of Bipolaris zeicola (Stout) Shoemaker (Manamgoda et al. 2014). For molecular identification, genomic DNA (isolate SU-11) was extracted and the internal transcribed spacer (ITS) region, large subunit (LSU) of ribosomal DNA, translation elongation factor (tef), glyceraldehyde 3-phosphate dehydrogenase (gpd), and RNA polymerase II second largest subunit (rpb2) genes were amplified and sequenced by using the primers ITS1-F/ITS4-R (White et al. 1990), LROR-F/LR5-R (Schoch et al. 2012), EF1-983F/EF1-2218R (Rehner and Buckley 2005), GPD1F/GPD2R (Berbee et al. 1999), and 5F2/7CR (O'Donnell et al. 2007), respectively. BLASTn searches showed 100% homology with the LSU and rpb2 sequences of B. zeicola (GenBank Accession Nos. MH876201 and HF934842) and 98-99% similarity with ITS, tef, and gpd sequences of B. zeicola (GenBank Accession Nos. KM230398, KM093752 and KM034815). The sequences of ITS, LSU, tef, gpd, and rpb2 were deposited in GenBank with accession numbers MN871712, MN877767, MN867685, MN904511 and MT349837, respectively. To fulfill Koch's postulates, 25 greenhouse-grown rice plants (cv. Basmati-385) at 2- to 3-leaf stage were spray inoculated with a spore suspension (105 spores/ml; isolate SU-11) prepared in SDW. Plants were covered with plastic wraps to maintain humid conditions for 24 hours and incubated at 27°C for one week. Similarly, ten non-inoculated plants sprayed with SDW served as controls. After one week, observed symptoms were similar to those from natural infections and no disease symptoms were observed on the non-inoculated plants. The experiment was repeated twice and the pathogen was re-isolated from the infected leaves and characterized morphologically. Globally, B. zeicola has also been reported to cause the leaf spot of rice and maize plants (Sivanesan 1987; Kang et al. 2018). To our information, this is the first report of B. zeicola causing brown leaf spot of rice in Pakistan. The increasing risk of this fungal pathogen in the rice-growing areas of Pakistan need a rigorous exploration and outreach effort to develop effective management practices.
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http://dx.doi.org/10.1094/PDIS-04-20-0838-PDNDOI Listing
August 2020

Wavelength dependent photo-cytotoxicity to ovarian carcinoma cells using temoporfin loaded tetraether liposomes as efficient drug delivery system.

Eur J Pharm Biopharm 2020 May 6;150:50-65. Epub 2020 Mar 6.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35037 Marburg, Germany. Electronic address:

5,10,15,20-Tetrakis(3-hydroxyphenyl)chlorin (mTHPC; temoporfin) is one of the most potent second-generation photosensitizers available today for the treatment of a variety of clinical disorders and has a unique capability of being activated at different wavelengths. However, due to its highly lipophilic nature, poor solubility in the aqueous media and poor bioavailability limits its application in anticancer therapies. To overcome these potential issues, we developed three different liposomal formulations with mTHPC encapsulated in hydrophobic milieu thus increasing the bioavailability of the drug. The prepared formulations were characterized in terms of hydrodynamic diameter, surface charge, encapsulation efficiency, and stability studies. The mean size of the liposomes was found to be in the nanoscale range (about 100 nm) with zeta potential ranging from -6.0 to -13.7 mV. mTHPC loaded liposomes were also evaluated for morphology using atomic force microscopy (AFM) and cryo-transmission electron microscopy (cryo-TEM). Data obtained from the hemocompatibility experiments showed that these formulations were compatible with blood showing less than 10% hemolysis and coagulation time lower than 40 s. The results obtained from the single-cell gel electrophoresis assay also demonstrated no incidence of genotoxicity. Photodynamic destruction of SK-OV-3 cells using mTHPC loaded liposomes showed a dose-response relationship upon irradiation with two different wavelength lights (blue λ = 457 nm & red λ = 652 nm). A 10-fold pronounced effect was produced when liposomal formulations were irradiated at 652 nm as compared to 457 nm. This was also evaluated by the quantitative assessment of reactive oxygen production (ROS) using fluorescence microscopy. The qualitative assessment of PDT pre- and post-irradiation was visualized using confocal laser scanning microscopy (CLSM) which demonstrated an intense localization of mTHPC liposomes in the perinuclear region. Chick chorioallantoic membrane assay (CAM) was used as an alternative in-ovo model to demonstrate the localized destruction of tumor microvasculature. Overall, the prepared nanoformulation is a biocompatible, efficient and well characterized delivery system for mTHPC for the safe and effective PDT.
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http://dx.doi.org/10.1016/j.ejpb.2020.03.008DOI Listing
May 2020

Development and Characterization of Bioadhesive Film Embedded with Lignocaine and Calcium Fluoride Nanoparticles.

AAPS PharmSciTech 2020 Jan 7;21(2):60. Epub 2020 Jan 7.

Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore Campus, Lahore, Pakistan.

The formation of biofilm by Streptococcus mutans on the tooth surface is the primary cause of dental caries and periodontal diseases, and fluoride (F) has shown tremendous potential as a therapeutic moiety against these problems. Herein, we report an efficient multi-ingredient bioadhesive film-based delivery system for oral cavity to combat dental problems with an ease of administration. Thiolated chitosan-based bioadhesive film loaded with calcium fluoride nanoparticles (CaF NPs) and lignocaine as a continuous reservoir for prolonged delivery was successfully prepared and characterized. The polygonal CaF NPs with an average particle size less than 100 nm, PDI 0.253, and + 6.10 mV zeta potential were synthesized and loaded in film. The energy dispersive x-ray (EDX) spectroscopy confirmed the presence 33.13% F content in CaF NPs. The characterization of the three film trials for their mechanical strength, bioadhesion, drug release, and permeation enhancement suggested film B as better among the three trials and showed significant outcomes, indicating the potential application of the medicated bioadhesive film. In vitro dissolution studies revealed sustained release pattern of lignocaine and CaF NP following Krosmeyer-Peppas model over 8 h. Franz diffusion studies showed the prolonged contact time of film with mucosa that facilitated the transport of CaF NPs and lignocaine across the mucosa. Hence, the prepared bioadhesive film-based system showed good potential for better management of dental problems. Graphical Abstract.
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http://dx.doi.org/10.1208/s12249-019-1615-5DOI Listing
January 2020

Targeted ErbB3 cancer therapy: A synergistic approach to effectively combat cancer.

Int J Pharm 2020 Feb 14;575:118961. Epub 2019 Dec 14.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany. Electronic address:

Surface modification of nanoparticles with aptamer is gaining popularity lately due to its selective targeting and low immunogenicity. In this study, sorafenib tosylate (SFB) was loaded in biodegradable PLGA nanoparticles prepared by solvent evaporation method. The surfaces of drug deprived and drug-loaded particles (PN and PNS, respectively) were coupled with aptamer to target ErbB3 using EDC/NHS chemical modification. Nanoparticles were characterized with regard to their size, shape and chemical composition by dynamic light scattering, atomic force microscopy, FTIR and elemental analysis respectively. To evaluate the particles in vitro cell culture studies were performed. Cell viability assay, pathway analysis and apoptosis assay showed cellular toxicity in the presence of aptamer in PNS-Apt (p < 0.001). Metastatic progression assay showed decreased cell migration in the presence of aptamer and SFB. Confocal laser scanning microscopy was used to visualize the receptor-mediated time-dependent intracellular uptake and distribution of the nanoparticles throughout the cytoplasm. The findings of the current study demonstrated the potential efficacy of the surface modified SFB-loaded particles against ErbB3.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118961DOI Listing
February 2020

Selective anti-ErbB3 aptamer modified sorafenib microparticles: In vitro and in vivo toxicity assessment.

Eur J Pharm Biopharm 2019 Dec 15;145:42-53. Epub 2019 Oct 15.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany. Electronic address:

The delivery of aptamer modified therapeutic moieties to specific tissue sites has become one of the major therapeutic choices to reduce the toxicity of inhibitory drugs. Bearing this in mind, the current study was designed using sorafenib (SFB) encapsulated microparticles (MP) prepared with biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) copolymer. The surfaces of these microparticles were modified with RNA aptamer having a binding affinity towards ErbB3 receptors. SFB-loaded MP (MPS) were prepared by o/w solvent evaporation method and the surface was coupled with the amino group of aptamer by EDC/NHS chemistry. Physiochemical investigations were done by dynamic light scattering, scanning electron microscopy and FTIR. In vitro apoptosis assay, cell viability assay and metastatic progression showed a significant decrease (p < 0.001) in vitro cell viability for MPS and MPS-Apt as compared to MP. The synergistic combination of SFB and aptamer also decreased the metastatic progression of cells for an extended period. Microparticles were also evaluated for in vivo toxicity in female BALB/c mice. It was evident that the presence of aptamer decreased the generalized toxicity of MPS-Apt, as measured by mean body weight loss and blood profiles, keeping all the blood formed elements level within acceptable limits. The histopathological investigations showed some necrotic and pyknotic bodies. In a similar fashion, liver function test and renal function tests showed pronounced effects of formulations on vital organs.
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http://dx.doi.org/10.1016/j.ejpb.2019.10.003DOI Listing
December 2019

Lipodendriplexes: A promising nanocarrier for enhanced gene delivery with minimal cytotoxicity.

Eur J Pharm Biopharm 2019 Feb 24;135:72-82. Epub 2018 Dec 24.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany. Electronic address:

Non-viral vectors are a safe, efficient and non-toxic alternative to viral vectors for gene therapy against many diseases ranging from genetic disorders to cancers. Polyamidoamine (PAMAM), a positively charged dendrimer has a tendency to complex with nucleic acids (to form dendriplexes) like plasmid DNA (pDNA) and small interfering RNA (siRNA) and can shield them from enzymatic degradation, thereby facilitating endocytosis and endosomal release. In this study, we developed an advanced variant of the dendriplexes by encapsulating them within liposomes to enhance their gene delivery efficiency. This liposome encapsulated dendriplex system can further reduce unwanted cytotoxicity and enhance cellular uptake of nucleic acids. A broad range of lipid combinations were used to optimize the lipodendriplexes in terms of their physicochemical characteristics including size, shape and zeta potential. The optimized lipodendriplexes were tested for pDNA transfection, in vitro cell viability, cellular uptake, siRNA mediated knockdown, hemocompatibility, metastatic progression and in ovo in chorioallantoic membrane model (CAM). The optimized system has shown significant improvement in pDNA transfection (p < 0.01) with higher GFP expression and gene silencing and has shown improved cell viability (p < 0.05) compared to the parent dendriplex system. The hemocompatibility and CAM analysis, revealed an efficient yet biocompatible gene delivery system in the form of lipodendriplexes.
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http://dx.doi.org/10.1016/j.ejpb.2018.12.013DOI Listing
February 2019

Prevalence of Extended Spectrum β-Lactamase and Antimicrobial Susceptibility Pattern of Clinical Isolates of Pseudomonas from Patients of Khyber Pakhtunkhwa, Pakistan.

Biomed Res Int 2016 5;2016:6068429. Epub 2016 Jun 5.

Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.

Majority of gram negative pathogenic bacteria are responsible for extended spectrum β-lactamases (ESBLs) production, which show resistance to some newer generation of antibiotics. The study was aimed at evaluating the prevalence of ESBL and antibiotic susceptibility pattern of Pseudomonas isolates collected during 2010 to 2014 from tertiary care hospitals of Peshawar, Pakistan. Out of 3450 samples, 334 Pseudomonas spp. isolates comprised of 232 indoor and 102 outdoor patients were obtained from different specimens and their susceptibility pattern was determined against 20 antibiotics. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer agar diffusion method and ESBL production was detected by Synergy Disc Diffusion technique. The mean age group of the patients was 29.9 + 9.15 years. Meronem showed best activity (91.02%) from class carbapenem, β-lactam and β-lactamase inhibitors exhibited 69.16% activity, and doxycycline had a diminished activity (10.18%) to Pseudomonas spp. Outdoor isolates were more resistant than the indoor and during the course of the study the sensitivity rate of antibiotics was gradually reducing. ESBL production was observed in 44.32% while the remaining was non-ESBL. The moderate active antibiotics were amikacin (50.7%), SCF (51.4%), TZP (52.7%), and MXF (54.1%) among ESBL producing isolates. Lack of antibiotic policy, irrational uses (3GCs particularly), and the emergence of antibiotic resistant organisms in hospitals may be causes of high antibiotic resistance.
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http://dx.doi.org/10.1155/2016/6068429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912991PMC
February 2017

Modelling and Bayesian adaptive prediction of individual patients' tumour volume change during radiotherapy.

Phys Med Biol 2016 Mar;61(5):2145-61

The aim of this study is to develop a mathematical modelling method that can predict individual patients’ response to radiotherapy, in terms of tumour volume change during the treatment. The main concept is to start from a population-average model, which is subsequently updated from an individual’s tumour volume measurement. The model becomes increasingly personalized and so too does the prediction it produces. This idea of adaptive prediction was realised by using a Bayesian approach for updating the model parameters. The feasibility of the developed method was demonstrated on the data from 25 non-small cell lung cancer patients treated with helical tomotherapy, during which tumour volume was measured from daily imaging as part of the image-guided radiotherapy. The method could provide useful information for adaptive treatment planning and dose scheduling based on the patient’s personalised response.
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http://dx.doi.org/10.1088/0031-9155/61/5/2145DOI Listing
March 2016

Preparation and Characterization of Solid Dispersions of Artemether by Freeze-Dried Method.

Biomed Res Int 2015 17;2015:109563. Epub 2015 May 17.

Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.

Solid dispersions of artemether and polyethylene glycol 6000 (PEG6000) were prepared in ratio 12 : 88 (group-1). Self-emulsified solid dispersions of artemether were prepared by using polyethylene glycol 6000, Cremophor-A25, olive oil, Transcutol, and hydroxypropyl methylcellulose (HPMC) in ratio 12 : 75 : 5 : 4 : 2 : 2, respectively (group-2). In third group, only Cremophor-A25 was replaced with Poloxamer 188 compared to group-2. The solid dispersions and self-emulsified solid dispersions were prepared by physical and freeze dried methods, respectively. All samples were characterized by X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimeter, scanning electron microscopy, and solubility, dissolution, and stability studies. X-ray diffraction pattern revealed artemether complete crystalline, whereas physical mixture and freeze-dried mixture of all three groups showed reduced peak intensities. In attenuated total reflectance Fourier transform infrared spectroscopy spectra, C-H stretching vibrations of artemether were masked in all prepared samples, while C-H stretching vibrations were representative of polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188. Differential scanning calorimetry showed decreased melting endotherm and increased enthalpy change (ΔH) in both physical mixture and freeze-dried mixtures of all groups. Scanning electron microscopy of freeze-dried mixtures of all samples showed glassy appearance, size reduction, and embedment, while their physical mixture showed size reduction and embedment of artemether by excipients. In group-1, solubility was improved up to 15 times, whereas group-2 showed up to 121 times increase but, in group-3, when Poloxamer 188 was used instead of Cremophor-A25, solubility of freeze-dried mixtures was increased up to 135 times. In fasted state simulated gastric fluid at pH 1.6, the dissolution of physical mixture was increased up to 12 times and freeze-dried mixtures up to 15 times. The stability of artemether was substantially enhanced in freeze-dried mixtures by using polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188 of self-emulsified solid dispersions of artemether in Hank's balanced salt solution at pH 7.4.
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http://dx.doi.org/10.1155/2015/109563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449868PMC
March 2016

Mathematical modelling of tumour volume dynamics in response to stereotactic ablative radiotherapy for non-small cell lung cancer.

Phys Med Biol 2015 May 17;60(9):3695-713. Epub 2015 Apr 17.

Department of Chemical and Process Engineering, University of Surrey, Guildford, GU2 7XH, UK.

This paper reports a modelling study of tumour volume dynamics in response to stereotactic ablative radiotherapy (SABR). The main objective was to develop a model that is adequate to describe tumour volume change measured during SABR, and at the same time is not excessively complex as lacking support from clinical data. To this end, various modelling options were explored, and a rigorous statistical method, the Akaike information criterion, was used to help determine a trade-off between model accuracy and complexity. The models were calibrated to the data from 11 non-small cell lung cancer patients treated with SABR. The results showed that it is feasible to model the tumour volume dynamics during SABR, opening up the potential for using such models in a clinical environment in the future.
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http://dx.doi.org/10.1088/0031-9155/60/9/3695DOI Listing
May 2015

Iron deficiency anaemia in reproductive age women attending obstetrics and gynecology outpatient of university health centre in Al-Ahsa, Saudi Arabia.

Afr J Tradit Complement Altern Med 2014 28;11(2):339-42. Epub 2014 Jan 28.

Department of Pharmaceutical Sciences.

Background: Iron deficiency is the most common nutritional disorder in the world. The aim of this questionnaire based survey study was to determine the prevalence of iron deficiency anemia in reproductive age women, and their relation to variables such as age, marital status, education with those attending obstetrics and gynecology outpatient of King Faisal University Health Centre in Al-Ahsa in eastern region of Kingdom of Saudi Arabia.

Materials And Methods: This study was conducted for the period of 6 month staring from September 2012 to February 2013. The questionnaire had three sections on personal information: their educational indicators, gynecological clinical history, and hematological indices.

Results: The average age was 25.97±7.17 years. According to the gynecological clinical history of the respondents, 15 (48.4%) respondents were pregnant while 16 (51.6%) were not pregnant. There was significant effect of pregnancy status on Hb level. Majority of the anemic respondents 15/17 were married. Moreover 14/17 anemic women were experiencing severe menstrual bleeding, 11/17 respondents were pregnant. 54.8% of respondents were hemoglobin deficient while 77.4% were found to have low Hct. In 87.1 % of the respondents, transferrin saturation was found to be abnormal.

Conclusion: In this study iron deficiency anemia is quite prevalent in the university community especially among pregnant women. The fetus's and newborn infant's iron status depends on the iron status of the pregnant woman and therefore, iron deficiency in the mother-to-be means that growing fetus probably will be iron deficient as well. Thus iron deficiency anemia during pregnancy in well-educated set up needs more attention by the concerned authorities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202643PMC
http://dx.doi.org/10.4314/ajtcam.v11i2.19DOI Listing
July 2015

Spectrophotometric method for the determination of Gemifloxacin mesylate in pure and tablet dosage form.

Pak J Pharm Sci 2014 Sep;27(5):1171-4

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

A spectrophotometric method for the determination of Gemifloxacin mesylate (GFX) is developed and validated according to ICH guidelines. GFX is a fluoroquinolone that is used in the treatment of pneumonia. The analysis of the pure drug was carried out at its λmax 270 nm. The method was linear from 0.5-5μg/mL, r(2) 0.999 and equation is 0.102-0.000. The % RSD for inter-day (0.969%) and intra-day (0.714%) assuring a good precision and accuracy was close to 100%. Limit of detection and Limit of quantification were 0.197 and 0.599μg/mL, respectively. The validation results and statistical data demonstrate that the method is accurate, sensitive, cost effective and reproducible and has an importance in quality assurance of GFX analysis. The developed method was proved suitable for analysis of GFX in the pure and tablet dosage forms without interference of excepients.
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September 2014

Current and future lymphatic imaging modalities for tumor staging.

Biomed Res Int 2014 16;2014:714674. Epub 2014 Mar 16.

Beijing University of Chinese Medicine, Dongzhimen Hospital, Dong Cheng District, Beijing 100700, China.

Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review.
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http://dx.doi.org/10.1155/2014/714674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976799PMC
December 2014

Hypoglycemic activity of Ficus racemosa bark in combination with oral hypoglycemic drug in diabetic human.

Acta Pol Pharm 2013 Nov-Dec;70(6):1045-9

Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.

Medicinal herbs, used in indigenous medicines in crude forms for the management of diabetes mellitus, contain both the organic and inorganic constituents. The aim of the study was to find out the hypoglycemic effect of Ficus racemosa in a group of diabetic subjects taking oral hypoglycemic drug. Twenty five of each, male and female, diabetic patients, selected from Fatima Jinnah Medical College, Lahore, Pakistan, taking oral hypoglycemic drug were included in this study and were given orally the extract (5 mL) of bark of Ficus racemosa (about 100 mg) two times for 15 days. Blood samples for estimation of blood glucose and parameters of liver and renal functions were estimated. It was observed that after taking the herb in combination with drug, blood glucose level (fasting and after breakfast) was markedly decreased in both male and female but significant difference was only observed in sugar level of males after 1.5 h after breakfast. To rule out herb toxicity, liver and renal functions tests of patients was also performed which were observed to be in normal range. Present investigation established a pharmacological evidence to support the folklore claim that Ficus racemosa is good anti-diabetic agent.
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February 2014

Malaria and artemisinin derivatives: an updated review.

Mini Rev Med Chem 2013 Nov;13(13):1879-902

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan, 60800.

Malaria is the world's most prevalent disease that affects 515-600 million people each year and about 40% of the world's population live at risk for this infection. The prevalence of morbidity and mortality from drug resistant malaria (Plasmodium falciparum) is increasing in most of the developing countries, which is also a global threat because international travel is common now and imported malaria is increasingly a serious problem. Since rapid schizonticidal action of naturally occurring endoperoxides pharmacophore present in artemisinin against drug-resistant malaria has been documented, researchers have focused more on artemisinin analogs than any other antimalarials. In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives (arteether, artemether, artemiside, artemisinin, artemisone, artesunate, dihydroartemisinin) have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.
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http://dx.doi.org/10.2174/13895575113136660097DOI Listing
November 2013