Publications by authors named "Mohamed M Badran"

20 Publications

  • Page 1 of 1

Crosstalk of low density lipoprotein and liposome as a paradigm for targeting of 5-fluorouracil into hepatic cells: cytotoxicity and liver deposition.

Bioengineered 2021 Dec;12(1):914-926

Prince Naif for the Health Research Center, King Saud University, Riyadh, Saudi Arabia.

This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 - 194 nm), negative zeta potential (- 0.82 to - 16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28-49 nm), negative zeta potential (- 17 to -27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway.
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http://dx.doi.org/10.1080/21655979.2021.1896202DOI Listing
December 2021

Improved pharmacokinetic and biodistribution of 5-fluorouracil loaded biomimetic nanoerythrocytes decorated nanocarriers for liver cancer treatment.

Colloids Surf B Biointerfaces 2021 Jan 4;197:111380. Epub 2020 Oct 4.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Pharmaceutics, College of Pharmacy, Al-Azhar University Cairo, Egypt. Electronic address:

Nanoerythrocytes membrane (NEs) has recently been used to improve pharmacokinetics and biodistribution for successful drug therapy. NEs intended to enhance the drug targeting due to immune evasion and long circulation. In this work, NEs could serve as efficient 5- fluorouracil (5-FU) carriers to target liver cells. NEs decorated 5-FU-loaded chitosan coated-poly (lactide-co-glycolic acid) nanoparticles (5-FU-C-NPs-NEs), chitosomes (5-FU-C-LPs-NEs) and 5-FU-NEs were prepared by hypotonic lysis and extrusion procedures. Moreover, 5-FU loaded-chitosan coated 5-FU-NPs (5-FU-C-NPs) and chitosomes (5-FU-C-LPs) for the compared issues were prepared. They were characterized in terms of particle size, encapsulation efficiency (EE), membrane protein content, phosphatidylserine exposure, surface morphology, and in vitro release profiles. Also, their cytotoxic efficacy was determined. Furthermore, pharmacokinetics and biodistribution studies were investigated for optimized formulation. The results revealed that 5-FU-C-NPs-NEs have narrow particle size distribution, desirable EE%, and retained the erythrocyte membrane properties as confirmed by polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, it displayed a sustained release profile up to 72 h of 5-FU-C-NPs-NEs compared to other formulations. In comparison to 5-FU solution and 5-FU-C-NPs, 5-FU-C-NPs-NEs extended the drug release time in vivo with highly uptake by the liver. These results suggest that the 5-FU-C-NPs-NEs could be used to deliver 5-FU and enhance its targetability to liver cancer.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111380DOI Listing
January 2021

Cytotoxicity of Chitosan Ultrafine Nanoshuttles on the MCF-7 Cell Line as a Surrogate Model for Breast Cancer.

Curr Drug Deliv 2021 ;18(1):19-30

Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Aim: This study aimed to explore an affordable technique for the fabrication of Chitosan Nanoshuttles (CSNS) at the ultrafine nanoscale less than 100 nm with improved physicochemical properties, and cytotoxicity on the MCF-7 cell line.

Background: Despite several studies reported that the antitumor effect of CS and CSNS could achieve intracellular compartment target ability, no enough information is available about this issue and further studies are required to address this assumption.

Objectives: The objective of the current study was to investigate the potential processing variables for the production of ultrafine CSNS (less than; 100 nm) using Box-Behnken Design factorial design (BBD). This was achieved through a study of the effects of processing factors, such as CS concentration, CS/TPP ratio, and pH of the CS solution, on PS, PDI, and ZP. Moreover, the obtained CSNS was evaluated for physicochemical characteristics, morphology. In addition, hemocompatibility and cytotoxicity using Red Blood Cells (RBCs) and MCF-7 cell lines were investigated.

Methods: Box-Behnken Design factorial design (BBD) was used in the analysis of different selected variables. The effects of CS concentration, sodium tripolyphosphate (TPP) ratio, and pH on particle size, Polydispersity Index (PDI), and Zeta Potential (ZP) were measured. Subsequently, the prepared CS nanoshuttles were exposed to stability studies, physicochemical characterization, hemocompatibility, and cytotoxicity using red blood cells and MCF-7 cell lines as surrogate models for study.

Result: The present results revealed that the optimized CSNS has ultrafine nanosize, (78.3 ± 0.22 nm), homogenous with PDI (0.131 ± 0.11), and ZP (31.9 ± 0.25 mV). Moreover, CSNS has a spherical shape, amorphous in structure, and physically stable. Moreover, CSNS has biological safety as indicated by a gentle effect on red blood cell hemolysis, besides, the obtained nanoshuttles decrease MCF-7 viability.

Conclusion: The present findings concluded that the developed ultrafine CSNS has unique properties with enhanced cytotoxicity, thus promising for use in intracellular organelles drug delivery.
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http://dx.doi.org/10.2174/1567201817666200719005440DOI Listing
January 2021

Lipoproteins-Nanocarriers as a Promising Approach for Targeting Liver Cancer: Present Status and Application Prospects.

Curr Drug Deliv 2020 ;17(10):826-844

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

The prevalence of liver cancer is increasing over the years and it is the fifth leading cause of mortality worldwide. The intrusive features and burden of low survival rate make it a global health issue in both developing and developed countries. The recommended chemotherapy drugs for patients in the intermediate and advanced stages of various liver cancers yield a low response rate due to the nonspecific nature of drug delivery, thus warranting the search for new therapeutic strategies and potential drug delivery carriers. There are several new drug delivery methods available to ferry the targeted molecules to the specific biological environment. In recent years, the nano assembly of lipoprotein moieties (lipidic nanoparticles) has emerged as a promising and efficiently tailored drug delivery system in liver cancer treatment. This increased precision of nano lipoproteins conjugates in chemotherapeutic targeting offers new avenues for the treatment of liver cancer with high specificity and efficiency. This present review is focused on concisely outlining the knowledge of liver cancer diagnosis, existing treatment strategies, lipoproteins, their preparation, mechanism and their potential application in the treatment of liver cancer.
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http://dx.doi.org/10.2174/1567201817666200206104338DOI Listing
January 2020

Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, and Assessment.

Front Pharmacol 2019 2;10:459. Epub 2019 May 2.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Health Sciences University, Clovis, CA, United States.

Objective: The aim of this study was to investigate the and performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL), a poorly water-soluble drug.

Methods: Self-nanoemulsifying drug delivery systems of TAL were prepared using various oils, non-ionic surfactants and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The dissolution experiments and human red blood cells (RBCs) toxicity test, gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum 50 mg and raw drug.

Results: The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release (>97% in 2.0 h) compared to raw TAL and marketed product Cordanum. The RBC lysis test suggested negligible toxicity of the formulation to the cells. The permeability assessment and pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four-fold increase in permeability and 1.58-fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively.

Conclusion: Talinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability.
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http://dx.doi.org/10.3389/fphar.2019.00459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507620PMC
May 2019

Nano-erythrocyte membrane-chaperoned 5-fluorouracil liposomes as biomimetic delivery platforms to target hepatocellular carcinoma cell lines.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):989-996

a Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.

Nano-erythrocyte coating has been developed as an interesting biomimetic platform to provide hybrid nano-carriers with innate functions to target liver cancer. This goal was achieved by coating nano-erythrocyte membranes (NEMs) onto 5-fluorouracil (5-FU)-loaded liposomes (LPs) to produce NEM-5-FU-LPs. This framework is used to promote the escape of 5-FU-LPs from degradation during systemic circulation. NEMs were obtained by hypotonic lysis of erythrocytes to produce ghost erythrocytes (GEs) followed by extrusion through polycarbonate membranes. Chimeric NEM-5-FU-LPs were fabricated via the fusion of NEMs and artificial LPs. The resultant chaperoned LPs were characterized based on particle size, morphology, entrapment efficiency (EE %), stability, protein content and phosphatidylserine exposure and their in vitro release profiles and cytotoxic efficacy were also determined. The present results revealed that 5-FU-LPs, NEM-5-FU and NEM-5-FU-LPs exhibited nanosize, spherical shapes and unimodal size distributions <0.3. In addition, the vesicles presented a zeta potential with EE% of 24.6-30.7% and an appropriate stability for 3 weeks. NEM-5-FU-LPs retained the erythrocyte membrane proteins as confirmed by PAGE and displayed a sustained release profile up to 48 h when compared to NEM-5-FU and the 5-FU solution. Moreover, hybrid NEM-5-FU-LPs induced a late cytotoxic effect after 48 h compared to the other formulations. Thus, mantling of 5-FU-LPs by NEMs could enhance vesicle controllability and their targetability to liver cancer cells.
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http://dx.doi.org/10.1080/21691401.2019.1577887DOI Listing
December 2019

Chitosan-Coated Flexible Liposomes Magnify the Anticancer Activity and Bioavailability of Docetaxel: Impact on Composition.

Molecules 2019 Jan 11;24(2). Epub 2019 Jan 11.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia.

Flexible liposomes (FLs) were developed as promising nano-carriers for anticancer drugs. Coating them with chitosan (CS) could improve their drug delivery properties. The aim of this study was to investigate the physicochemical characteristics, pharmacokinetics behavior, and cytotoxic efficacy of docetaxel (DTX)-loaded CS-coated FLs (C-FLs). DTX-loaded FLs and C-FLs were produced via thin-film evaporation and electrostatic deposition methods, respectively. To explore their physicochemical characterization, the particle size, zeta potential, encapsulation efficiency (EE%), morphology, and DTX release profiles were determined. In addition, pharmacokinetic studies were performed, and cytotoxic effect was assessed using colon cancer cells (HT29). Various FLs, dependent on the type of surfactant, were formed with particle sizes in the nano-range, 137.6 ± 6.3 to 238.2 ± 14.2 nm, and an EE% of 59⁻94%. Moreover, the zeta potential shifted from a negative to a positive value for C-FL with increased particle size and EE%, and the in vitro sustained-release profiles of C-FL compared to those of FL were evident. The optimized C-FL containing sodium deoxycholate (NDC) and dicetyl phosphate (DP) elicited enhanced pharmacokinetic parameters and cytotoxic efficiency compared to those of the uncoated ones and Onkotaxel. In conclusion, this approach offers a promising solution for DTX delivery.
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http://dx.doi.org/10.3390/molecules24020250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359228PMC
January 2019

Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, Dispersion, Digestion and Gut Permeation Studies.

Front Pharmacol 2018 6;9:1219. Epub 2018 Nov 6.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

The choice of lipid excipients and their origin are crucial determinant factors in the design of self-nanoemulsifying drug delivery system (SNEDDS). To investigate the aspects of alternative excipients which can influence the development of efficient SNEDDS and determine the fate of fenofibrate in aqueous media. SNEDDS of two groups (a and b) were developed using Cremercoor MCT/Capmul MCM and Kollisolv MCT/Imwitor 742 blended oils and water soluble surfactants (to improve lipid polarity) for the model anti-cholesterol drug fenofibrate. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEDDS. Further SNEDDS optimizations were done on the basis of maximum drug loading by equilibrium solubility studies and maximum solubilized drug upon aqueous dispersion by dynamic dispersion studies. lipolysis was examined under simulated Fed and Fasted conditions. Intestinal permeability study of the optimal SNEDDS formulation was compared with the raw fenofibrate dispersion using non- everted "intestinal sac technique." Initial characterization and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 (group b) containing formulations generated highly efficient SNEDDS as they are stable and produced lower nanodroplets with higher drug loading (group b) as compared to mixed glycerides of Cremercoor MCT/Capmul MCM (group a). dispersion and digestion studies confirmed that SNEDDS of group b (polar mixed glycerides) can retain high amount of drug (99% drug in solution for more than 24 h time) in dispersion media and have high recovery after digestion. The results from the permeability assessment confirmed that fenofibrate had 4.3-fold increase with F3b SNEDDS compared with the control. SNEDDS formulations containing alternative excipients (Kollisolv MCT/Imwitor 742 blend) could be a potential oral pharmaceutical product in taking anti-hyperlipidaemic agent fenofibrate to the systemic circulation as solubilized form.
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http://dx.doi.org/10.3389/fphar.2018.01219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232043PMC
November 2018

Multifunctional carbamazepine loaded nanostructured lipid carrier (NLC) formulation.

Int J Pharm 2018 Oct 1;550(1-2):359-371. Epub 2018 Sep 1.

Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, P.O. Box 2014, Skaka, Saudi Arabia.

Carbamazepine is a valuable pharmacological agent prescribed in treatment of epilepsy and trigeminal neuralgia. Poor bioavailability, successive dose adjustments and reported long term toxic effects are the main hurdles associated with carbamazepine oral administration. Bees wax containing NLC formulations were developed using high shear homogenization/sonication technique to overcome drug limitations. Formulations were successfully produced and evaluated for both in vitro and in vivo assessments. Results showed particles in nanometric range with negative surface charge and satisfying encapsulation efficiencies (from 93.1 ± 7.6 to 95.7 ± 5.6%). In vitro release studies revealed biphasic pattern and faster release was accompanied with higher bees wax concentration. Interaction between drug and NLC components was assessed using infrared and thermal analysis. Using validated chromatographic analytical method, selected formulation showed good pharmacokinetic profile depriving from plasma fluctuation with 2.27-fold and 1.83-fold improved bioavailability compared to conventional drug suspension and Tegretol™ suspension respectively. It also showed stronger anticonvulsant activity, with respect to conventional drug suspension, in terms of seizure latency, frequency and duration. Toxicity studies revealed undetectable liver or testicular toxicity in biochemical, histological and immunohistochemical investigations verifying its superiority above other investigated formulations. Collectively, results indicate potential suitability of NLC system to effectively and safely deliver carbamazepine orally.
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http://dx.doi.org/10.1016/j.ijpharm.2018.08.062DOI Listing
October 2018

Crosstalk of Nanosystems Induced Extracellular Vesicles as Promising Tools in Biomedical Applications.

J Membr Biol 2017 12 10;250(6):605-616. Epub 2017 Nov 10.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Hybrid vesicles are considered as a bridge between natural nanosystems (NNSs) and artificial nanosystems (ANSs). NNSs are extracellular vesicles (EVs), membranous, bio-formed endogenously, which act as endogenous cargoes, and reflecting cellular dynamics. EVs have cellular tropism, permeate tight junctions, and are non-immunogenic. EVs are used as tools in the development of diagnostic and therapeutic agents. ANSs can induce biogenesis of hybrid vesicles as promising smart diagnostic agents, and innovative drug cargoes. EVs can encapsulate small molecules, macromolecules, and ANSs. The manipulation of EVs during biogenesis was suggested for engineering hybrid EVs. This review article highlights the role of ANSs in the biogenesis of NNSs, and introduces hybrid nanosystems research.
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http://dx.doi.org/10.1007/s00232-017-0003-xDOI Listing
December 2017

An overview of nanosomes delivery mechanisms: trafficking, orders, barriers and cellular effects.

Artif Cells Nanomed Biotechnol 2018 Jun 13;46(4):669-679. Epub 2017 Jul 13.

e Department of Pharmacology and Toxicology , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia.

This review traces the journey of nanosomes from administration until elimination, and discusses various biological barriers. The nanosomes are imported into the body through different routes and are localized into specified organ, cell, subcellular locations or organelle compartment. The nanosomes delivery to a specific destination depends on the surface chemistry, size, shape and the presence of specific ligands. Endocytosis/exocytosis cycles are involved in the import and export of the nanosomes. The mononuclear phagocytic system and ATP-binding cassette are universal checkpoints for nanosomes trafficking. The gastrointestinal milieu is the checkpoints for orally administered nanosomes. The mucociliary escalator is a specialized obstacle for inhaled nanosomes. Dermally applied nanosomes are tackled by Langerhans cells and keratinocytes. The nanosomes intended for subcellular destinations are mainly intercepted by lysosomes. Thus, nanosomes intended for biological administration must be designed to escape various barriers. The nanosomes affect cells function by alteration of redox status, and calcium signalling, ultimately, they are exocytosed from the cells.
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http://dx.doi.org/10.1080/21691401.2017.1354301DOI Listing
June 2018

Erythrocyte nanovesicles: Biogenesis, biological roles and therapeutic approach: Erythrocyte nanovesicles.

Saudi Pharm J 2017 Jan 2;25(1):8-17. Epub 2015 Jul 2.

Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

Nanovesicles (NVs) represent a novel transporter for cell signals to modify functions of target cells. Therefore, NVs play many roles in both physiological and pathological processes. This report highlights biogenesis, composition and biological roles of erythrocytes derived nanovesicles (EDNVs). Furthermore, we address utilization of EDNVs as novel drug delivery cargo as well as therapeutic target. EDNVs are lipid bilayer vesicles rich in phospholipids, proteins, lipid raft, and hemoglobin. In vivo EDNVs biogenesis is triggered by an increase of intracellular calcium levels, ATP depletion and under effect of oxidative stress conditions. However, in vitro production of EDNVs can be achieved via hypotonic treatment and extrusion of erythrocyte. NVs can be used as biomarkers for diagnosis, monitoring of therapy and drug delivery system. Many therapeutic agents are suggested to decrease NVs biogenesis.
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http://dx.doi.org/10.1016/j.jsps.2015.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310160PMC
January 2017

Preparation and characterization of polymeric nanoparticles surface modified with chitosan for target treatment of colorectal cancer.

Int J Biol Macromol 2017 Feb 28;95:643-649. Epub 2016 Nov 28.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Center of Excellence in Biotechnology Research (CEBR), King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia. Electronic address:

5-Fluorouracil (5-FU) loaded chitosan (C) coated polylactic-co-glycolic acid (PLGA) nanoparticles [NPs] (C-5-FU PLGA NPs) and polycaprolactone [PCL] (C-5-FU PCL NPs) were employed as the carriers for cancer treatment. The prepared NPs showed the spherical shape of NPs with the particle size in the range of 188.1-302.2nm with polydispersity index (PDI) of <0.30. C-coated NPs converted zeta potential from negative to positive value with small modification in particle size distribution. The entrapment efficiency of 5-FU was recorded in the range of 32-51%. The in vitro release studies showed an initial rapid 5-FU release followed by a sustained release profile. The in vitro cytotoxicity of C-5-FU PLGA NPs showed significant inhibition of colon cancer cells (HT-29) compared to the other NPs and drug solution. These results showed that C-5-FU PLGA NPs can be considered as a promising carrier for cancer therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.11.098DOI Listing
February 2017

Simvastatin-loaded nanostructured lipid carriers attenuate the atherogenic risk of erythrocytes in hyperlipidemic rats.

Eur J Pharm Sci 2017 Jan 7;96:62-71. Epub 2016 Sep 7.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address:

This study aimed to investigate the effect of simvastatin (SV) loaded nanostructured lipid carriers (SV loaded NLCs) on atherogenic index (AI), erythrocytes membrane lipid and antioxidant/pro-oxidant status in hyperlipidemic rats. SV loaded NLCs were successfully prepared with desired nano-particles size, spherical shape, high encapsulation efficiency (EE %) and sustained SV release. The results of biological studies revealed that administration of SV loaded NLCs to rats increased SV bioavailability compared to SV suspension. Intraperitoneal injection of tyloxapol as hyperlipidemic agent induces a significant increase of plasma AI, uric acid, lipid peroxidation and protein oxidation. While, plasma total antioxidant capacity and paraoxonase-1 activity were significantly decreased. Moreover, tyloxapol induced-hyperlipidemia increases erythrocyte's membrane cholesterol and deteriorates erythrocyte's antioxidant enzyme activity, GSH/GSSG ratio and NO level However, the propagation of erythrocyte's pro-oxidant activity and hemolysis was observed. On the contrast, the treatment of these rats with SV loaded NLCs improved the measured parameters compared to rats received SV suspension and hyperlipidemic rats. The predominant effect of SV loaded NLCs may be attributed to the enhancement of absorption, prolonged duration and improvement of bioavailability of SV. Accordingly, SV loaded NLCs showed advantageous effects on the blood lipid levels and atherogenic risk of erythrocytes in hyperlipidemic conditions compared to SV suspension.
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http://dx.doi.org/10.1016/j.ejps.2016.09.004DOI Listing
January 2017

Flexosomes for transdermal delivery of meloxicam: characterization and antiinflammatory activity.

Artif Cells Nanomed Biotechnol 2017 Mar 28;45(2):305-312. Epub 2016 Feb 28.

a Department of Pharmaceutics, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.

The study aims to investigate the impact of flexosomes (FLs) on transdermal delivery of meloxicam (MLX). FLs are composed of phospholipid, Tween 80, and ethanol which were prepared by film hydration method. The prepared FLs were characterized for particle size, zeta potential, and entrapment efficiency (EE). Ex vivo skin penetration studies were perfomed, and the best formulation was further evaluated using in vivo antiinflammatory activity test. FLs were in nano-size scale carring negative charge and observed high EE% and enhanced skin penetration of MLX compared to conventional liposomes (CLs). The best formula was FL4 which was composedof phospholipid (10%), Tween 80 (1.5%), and ethanol (40%). FL4 showed 143.4 nm vesicle size, 84% EE, and 31-fold ex vivo permeation enhancement through skin compared to CLs. The antiinflammatory activity of FL4 gel showed significant increase compared to control. This study observed the effectiveness of using FLs as carriers for transdermal delivery of MLX.
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http://dx.doi.org/10.3109/21691401.2016.1147452DOI Listing
March 2017

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

Saudi Pharm J 2016 Jan 21;24(1):74-81. Epub 2015 Mar 21.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.
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http://dx.doi.org/10.1016/j.jsps.2015.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720020PMC
January 2016

Reutilization of Tacrolimus Extracted from Expired Prograf® Capsules: Physical, Chemical, and Pharmacological Assessment.

AAPS PharmSciTech 2016 Aug 16;17(4):978-87. Epub 2015 Oct 16.

Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.

In this study, we investigated whether tacrolimus extracted and purified from the commercial capsules (Prograf® 5 mg) have retained its original quality and activity beyond the capsules expiration date in order to be reused for research purposes after extraction. High-performance liquid chromatography (HPLC) assay method was developed and validated for the quantification of tacrolimus, using cyclosporine A as an internal standard (IS). Moreover, a combination of analytical methods, including nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), Fourier transform-infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) were used to assess the quality of extracted/purified tacrolimus. Suppression of murine peripheral-blood mononuclear cells (PBMC) proliferation and the levels of interleukin-2 (IL-2) and interferon gamma (IFN-γ) were also assessed. The data obtained showed no detectable differences in the quality profile between the authentic sample and extracted drug. Also, the results showed that the extracted/purified tacrolimus was able to suppress T cell proliferation, induced by concanavalin A, indicating the retained pharmacological activity. We proved that tacrolimus extracted/purified from expired Prograf® capsuled retains its purity and immunosuppressive activity and can be reused for research and possibly in pharmaceutical manufacturing.
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http://dx.doi.org/10.1208/s12249-015-0433-7DOI Listing
August 2016

Fast ultra-fine self-nanoemulsifying drug delivery system for improving in vitro gastric dissolution of poor water soluble drug.

Acta Pol Pharm 2015 Jan-Feb;72(1):171-8

Meloxicam (MLX) has poor water solubility which leads to slow absorption following oral administration; hence, immediate release tablet is unsuitable in the treatment of acute pain. The aim of this study was to prepare a novel fast ultra-fine self-nanoemulsifying drug delivery system (UF-SNEDDS) of MLX for oral administration to facilitate drug release process in the stomach as well as comparing its in vitro dissolution with commercial Mobic and Mobitil tablets. MLX solubility in oils, mixed glycerides and surfactants with different HLB values was investigated. Based on MLX solubility profiles, eight UF-SNEDDSs composed of MLX, Cremophor RH 40 as oily phase, Capmul MCM-C8 or Tween 80 as surfactant and PEG 400 as co-solvent were prepared and evaluated for their spontaneous formation of emulsion, droplet size, turbidity and in vitro dissolution. The prepared novel MLX formulations showed a significant very low droplets size (up to 25 nm), thermodynamically stable and spontaneously formed nanoemulsion. MLX UF-SNEDDS formulations showed significant high percentage of drug dissolution (up to 70%) in simulated gastric fluid, compared with Mobic and Mobitil. In conclusion, due to higher drug release from MLX UF-SNEDDS formulations they could enhance its absorption and hence its bioavailability.
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April 2015

Evaluation of skin permeation and analgesic activity effects of carbopol lornoxicam topical gels containing penetration enhancer.

ScientificWorldJournal 2014 19;2014:127495. Epub 2014 Jun 19.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm(2)/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation.
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http://dx.doi.org/10.1155/2014/127495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089842PMC
March 2015

Itraconazole-hydroxypropyl-β-cyclodextrin loaded deformable liposomes: in vitro skin penetration studies and antifungal efficacy using Candida albicans as model.

Colloids Surf B Biointerfaces 2014 Sep 2;121:74-81. Epub 2014 Jun 2.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address:

The study aimed to develop novel ITZ-loaded deformable liposomes (DL) in presence of hydroxypropyl-β-cyclodextrin (HPβCD) (DL-CD) to enhance antifungal activity. These formulations have been reported as conceivable vesicles to deliver drug molecules to the skin layers. The efficiency of the prepared systems was compared with conventional liposomes (CL) and ITZ solution. The developed liposomes were characterized for particle size, entrapment efficiency (EE %), deformability, stability, and morphology of the vesicles. In addition, ex vivo penetration and antifungal activity were evaluated. It was found that the presence of HPβCD played a significant role in reducing the vesicle size to nano range. The deformability study and TEM images revealed that membrane deformability of DL and DL-CD was much higher than that of CL. Moreover, DL-CD enhanced the amount of ITZ in SC and deeper skin layers compared to DL and CL. The antifungal activity of ITZ-loaded deformable liposomes remained intact compared to ITZ solution. It can be concluded that deformable liposomes in the presence of HPβCD may be a promising carrier for effective cutaneous delivery of ITZ.
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http://dx.doi.org/10.1016/j.colsurfb.2014.05.030DOI Listing
September 2014