Wahid Khan | NIPER (National Institute of Pharmaceutical Education and Research) (original) (raw)

Papers by Wahid Khan

Pharmaceutics, 2017

Liposomes are the first nano drug delivery systems that have been successfully translated into re... more Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil ® , Ambisome ® , DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

Journal of drug targeting, Jan 29, 2015

Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders.... more Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain v...

Journal of Nanoparticle Research, 2015

ABSTRACT Dendrimers are discrete nanostructures/nanoparticles are emerging as promising candidate... more ABSTRACT Dendrimers are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FTIR spectroscopy. In vitro release of drug from DTX loaded pHBA conjugated dendrimer (CDN) was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

Drug Delivery, 2015

P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when usin... more P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

Evidence-Based Complementary and Alternative Medicine, 2015

Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections ... more Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail.

International journal of pharmaceutics, Jan 31, 2015

Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonsp... more Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using ph...

Chemistry and physics of lipids, Jan 25, 2015

Lipidic systems are considered to be the most promising carrier for drug delivery to brain. Metab... more Lipidic systems are considered to be the most promising carrier for drug delivery to brain. Metabolic substrates like carbohydrates and amino acids are able to traverse the blood-brain barrier (BBB) by specific carrier-mediated transport systems like glucose transporters present on the both luminal and abluminal side of the BBB. With this objective, the docetaxel (DTX) loaded solid lipidic nanoparticles were formulated and surface modified with a mannose derived ligand p-aminophenyl-α-d-mannopyranoside (MAN) to develop MAN conjugated lipidic nanoparticles for targeting DTX to brain. Lipidic nanoparticles were prepared using emulsification and solvent evaporation method using stearic acid as charge modifying lipid and conjugated with MAN using carbodimide coupling. These lipidic nanoparticles were successfully characterized using various techniques like DLS, TEM, DSC and FTIR spectroscopy. Cytotoxicity and cell uptake unveiled enhanced efficacy of conjugated lipidic nanoparticles. Ph...

International journal of pharmaceutics, 2012

Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye diseas... more Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye disease, and is available commercially as ophthalmic emulsion formulation (RESTASIS(®)). For increasing efficacy, and for reducing local toxicity including irritation to eyes, CsA nanosphere (CsA-NS) formulation was prepared and evaluated, in this work. CsA-NS formulation was prepared in a pre-concentrate form, which is a homogeneous solution of a CsA in a mixture of surfactants, lipids and solvents and provides nanosphere dispersion when added to aqueous medium. CsA-NS formulation was characterized and adjusted for particle size, pH, and osmolarity, suitable for ophthalmic administration. Thereafter, CsA-NS formulation was evaluated for parameters like irritation to eyes and penetrability of CsA in the rabbit eyes. Results obtained demonstrated that proposed CsA-NS formulation causes less irritation in rabbit eyes, with nearly same CsA penetration in the rabbit eyes in comparison to marketed ...

Advances in Delivery Science and Technology, 2013

ABSTRACT The area of polymer–drug conjugates is expanding spectacularly in recent years. From mac... more ABSTRACT The area of polymer–drug conjugates is expanding spectacularly in recent years. From macromolecular prodrugs of established anticancer agents to novel targeted polymeric drug conjugate systems, their application has expanded exponentially. Delivery of new anticancer agents, combination therapies, treatment of diseases other than cancer, and novel polymer architectures are highly exciting and promising areas. It is hoped that in the next decade, some of these new approaches will reach clinical evaluation and few will see the light of marketing phase. The successful development of first-generation polymer–drug conjugates in the mid-1980s and 1990s has inspired more recent studies assessing their potential as drug delivery platforms for combination therapy. These early works unveiled unexpected therapeutic benefits but raised new issues, in particular in relation to “system design.” A better understanding of how drug combinations impact on cellular and molecular mechanisms is needed to rationally design new therapeutics. In nutshell it is to be believed that the interdisciplinary scientific approach to the applications of polymer–drug conjugate (PDC) will result in their translation into the clinic within this decade.

Advances in Delivery Science and Technology, 2013

International Journal of Pharmaceutics, 2013

a b s t r a c t Cardiovascular diseases (CVD) are one of the leading causes of death across the g... more a b s t r a c t Cardiovascular diseases (CVD) are one of the leading causes of death across the globe. Pathogenesis of coronary artery disease (CAD) is lead by the progression of atherosclerotic lacerations in coronary arteries. Percutaneous coronary intervention (PCI) using balloon angioplasty was introduced in 1979 and was majorly used in the treatment of these lesions. Introduction of bare metal stents (BMS) has revolutionized stenting procedures overcoming elastic recoil and reducing restenosis commonly associated with balloon angioplasty, but follow up studies have shown 20-30% prevalence of in-stent restenosis (ISR), this led to the development of drug eluting stents (DES). But long-term follow up studies have shown increased liability of stent thrombosis. Boosting the development of safer and effective DES expounding for therapies like biodegradable polymer based DES, polymer free DES, bioresorbable DES and combination DES to collectively reduce neointimal hyperplasia and promote endothelial healing. In dual-DES development, a combination employing an anti-restenotic agent (for preventing VSMC's proliferation), which is released for the first few weeks, and then the second drug a pro-healing agent (promoting re-endothelialization) released after a month would be ideal. Growing understanding in the areas of polymer therapeutics, nanoscale surface modifications and gene therapy would assist in the delivery of multiple drugs, which would further help in the design of promising therapeutic strategies for the treatment of CAD using stent based therapies.

Advances in Delivery Science and Technology, 2014

Pharmaceutics, 2017

Liposomes are the first nano drug delivery systems that have been successfully translated into re... more Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil ® , Ambisome ® , DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

Journal of drug targeting, Jan 29, 2015

Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders.... more Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain v...

Journal of Nanoparticle Research, 2015

ABSTRACT Dendrimers are discrete nanostructures/nanoparticles are emerging as promising candidate... more ABSTRACT Dendrimers are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FTIR spectroscopy. In vitro release of drug from DTX loaded pHBA conjugated dendrimer (CDN) was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

Drug Delivery, 2015

P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when usin... more P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

Evidence-Based Complementary and Alternative Medicine, 2015

Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections ... more Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail.

International journal of pharmaceutics, Jan 31, 2015

Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonsp... more Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using ph...

Chemistry and physics of lipids, Jan 25, 2015

Lipidic systems are considered to be the most promising carrier for drug delivery to brain. Metab... more Lipidic systems are considered to be the most promising carrier for drug delivery to brain. Metabolic substrates like carbohydrates and amino acids are able to traverse the blood-brain barrier (BBB) by specific carrier-mediated transport systems like glucose transporters present on the both luminal and abluminal side of the BBB. With this objective, the docetaxel (DTX) loaded solid lipidic nanoparticles were formulated and surface modified with a mannose derived ligand p-aminophenyl-α-d-mannopyranoside (MAN) to develop MAN conjugated lipidic nanoparticles for targeting DTX to brain. Lipidic nanoparticles were prepared using emulsification and solvent evaporation method using stearic acid as charge modifying lipid and conjugated with MAN using carbodimide coupling. These lipidic nanoparticles were successfully characterized using various techniques like DLS, TEM, DSC and FTIR spectroscopy. Cytotoxicity and cell uptake unveiled enhanced efficacy of conjugated lipidic nanoparticles. Ph...

International journal of pharmaceutics, 2012

Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye diseas... more Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management of dry eye disease, and is available commercially as ophthalmic emulsion formulation (RESTASIS(®)). For increasing efficacy, and for reducing local toxicity including irritation to eyes, CsA nanosphere (CsA-NS) formulation was prepared and evaluated, in this work. CsA-NS formulation was prepared in a pre-concentrate form, which is a homogeneous solution of a CsA in a mixture of surfactants, lipids and solvents and provides nanosphere dispersion when added to aqueous medium. CsA-NS formulation was characterized and adjusted for particle size, pH, and osmolarity, suitable for ophthalmic administration. Thereafter, CsA-NS formulation was evaluated for parameters like irritation to eyes and penetrability of CsA in the rabbit eyes. Results obtained demonstrated that proposed CsA-NS formulation causes less irritation in rabbit eyes, with nearly same CsA penetration in the rabbit eyes in comparison to marketed ...

Advances in Delivery Science and Technology, 2013

ABSTRACT The area of polymer–drug conjugates is expanding spectacularly in recent years. From mac... more ABSTRACT The area of polymer–drug conjugates is expanding spectacularly in recent years. From macromolecular prodrugs of established anticancer agents to novel targeted polymeric drug conjugate systems, their application has expanded exponentially. Delivery of new anticancer agents, combination therapies, treatment of diseases other than cancer, and novel polymer architectures are highly exciting and promising areas. It is hoped that in the next decade, some of these new approaches will reach clinical evaluation and few will see the light of marketing phase. The successful development of first-generation polymer–drug conjugates in the mid-1980s and 1990s has inspired more recent studies assessing their potential as drug delivery platforms for combination therapy. These early works unveiled unexpected therapeutic benefits but raised new issues, in particular in relation to “system design.” A better understanding of how drug combinations impact on cellular and molecular mechanisms is needed to rationally design new therapeutics. In nutshell it is to be believed that the interdisciplinary scientific approach to the applications of polymer–drug conjugate (PDC) will result in their translation into the clinic within this decade.

Advances in Delivery Science and Technology, 2013

International Journal of Pharmaceutics, 2013

a b s t r a c t Cardiovascular diseases (CVD) are one of the leading causes of death across the g... more a b s t r a c t Cardiovascular diseases (CVD) are one of the leading causes of death across the globe. Pathogenesis of coronary artery disease (CAD) is lead by the progression of atherosclerotic lacerations in coronary arteries. Percutaneous coronary intervention (PCI) using balloon angioplasty was introduced in 1979 and was majorly used in the treatment of these lesions. Introduction of bare metal stents (BMS) has revolutionized stenting procedures overcoming elastic recoil and reducing restenosis commonly associated with balloon angioplasty, but follow up studies have shown 20-30% prevalence of in-stent restenosis (ISR), this led to the development of drug eluting stents (DES). But long-term follow up studies have shown increased liability of stent thrombosis. Boosting the development of safer and effective DES expounding for therapies like biodegradable polymer based DES, polymer free DES, bioresorbable DES and combination DES to collectively reduce neointimal hyperplasia and promote endothelial healing. In dual-DES development, a combination employing an anti-restenotic agent (for preventing VSMC's proliferation), which is released for the first few weeks, and then the second drug a pro-healing agent (promoting re-endothelialization) released after a month would be ideal. Growing understanding in the areas of polymer therapeutics, nanoscale surface modifications and gene therapy would assist in the delivery of multiple drugs, which would further help in the design of promising therapeutic strategies for the treatment of CAD using stent based therapies.

Advances in Delivery Science and Technology, 2014