Publications (8)5.56 Total impact
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Article: Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium
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ABSTRACT: The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%–82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12–16 hours). Cmax values of MVL formulations were significantly less (8.6–11.4 μg/mL) than MLV and free drug solution (12.5 μg/mL). The AUC0–48 of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in Cmax reflects that the MVL formulations could reduce the toxic complications and limitations of conventional IV and oral therapies.AAPS PharmSciTech 04/2012; 6(1):E35-E41. · 1.43 Impact Factor -
Article: Chondroitin sulfate functionalized liposomes for solid tumor targeting.
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ABSTRACT: The present investigation was aimed to develop and explore the use of chondroitin sulfate-coupled liposomes (CS-LP) for solid tumor targeting. The liposomes were prepared by cast film method and coupled with chondroitin sulfate. The coupling was confirmed by infrared spectroscopy. They were further characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, zeta potential, entrapment efficiency, and in vitro release pattern. The vesicle size of the uncoupled liposome (256 nm) was found to be less than that of CS-LP (310 nm). In vitro drug release exhibited a release of 44.2% from uncoupled liposomal formulation, compared to 38.3% as observed in coupled formulation at the end of 24 hr. The uptake of the CS-LP and uncoupled liposomes by MDA-MB-231 breast cancer cell lines was visualized using fluorescence microscopy that revealed the dependence of liposomes recognition and higher uptake on the coupling of chondroitin sulfate. Coupling of the liposomes significantly enhanced the tumor uptake of drug, which is reflected in the recovery of a higher percentage of the dose from tumor following administration of CS-LP in comparison to uncoupled liposomes or free drug, suggesting that they can be used as vectors for solid tumor targeting.Journal of Drug Targeting 05/2011; 19(4):251-7. · 2.70 Impact Factor -
Article: Bioconjugates: harnessing potential for effective therapeutics.
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ABSTRACT: The accomplishment of selective delivery can be brought through efficient drug targeting in which the attack of drug moiety is visualized only by the diseased organ and not by the organs of the whole body. This, in turn, consequently minimizes the unwanted effects or side effects caused by the drug action on the other organs. Bioconjugation is a fascinating technique that explores new vistas of drug delivery, and at the same time opens new possibilities for safe and effective therapy. This review is dedicated to and describes the science of bioconjugation and its potential in the drug delivery field, including different bioconjugates and their use in various therapeutic strategies. These have been classified as polymer based, macromolecule based, carrier based, and novel bioconjugates. This review describes the utility of bioconjugates in major diseases like cancer and others, and discusses experiments and research on the same. Bioconjugates have immense potential and extend a promising future in the drug delivery field. The review can act as a quick reference for those actively engaged in drug delivery and drug research to help overcome the hurdles of therapeutics.Critical reviews in therapeutic drug carrier systems. 02/2009; 26(2):119-55. -
Article: Steroid receptors as molecular targets for cancer diagnosis and therapy.
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ABSTRACT: The targeted delivery of chemotherapeutics is essential to minimizing the side effects by sparing the normal tissues by exposure to cytotoxic agents. The various receptors are overexpressed on the surface of the tumor tissues as compared to the normal tissues because their requirement for various essential components is high for the growth and development of tumor tissues. These overexpressed receptors on the tumor surface have been investigated for selective delivery of imaging, cytotoxic, or other therapeutic agents. Hormonal receptors viz. peptide and steroid receptors (SRs), which are present over the tumor surface, are also used for tumor targeting of various molecules for therapeutic use or imaging purpose. The key role of SRs is in the transactivation step of protein synthesis and to maintain the homeostasis in normal and diseased states. These receptors are overactivated in different diseases, including tumorigenesis. Hence, these SRs may act as a potential target for selective delivery of different therapeutic or cytotoxic agents. The selective delivery of these agents may be a better treatment strategy for endocrine cancer because it results in cytosolic and nuclear delivery of cytotoxic agents as well. The objective of the present review is to explore the importance of sex SRs as a vital target in endocrine cancer therapy. Potential strategies investigated for the delivery of imaging agents, chemotherapeutics, and toxins via steroidal ligands have been discussed. The importance of gene therapy in different diseases, including endocrine cancer, is well defined; thus, some effective gene delivery approaches investigated in endocrine cancer via steroidal ligands have also been discussed.Critical reviews in therapeutic drug carrier systems. 01/2009; 26(3):207-73. -
Article: Transferrin Coupled Liposomes for Enhanced Brain Delivery of Doxorubicin
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ABSTRACT: The objective of this study was to achieve enhanced delivery of doxorubicin to the brain through transferrincoupled liposomes. Doxorubicin-loaded liposomes were prepared and characterized for particle size, shape, percent encapsulation efficiency and in vitro drug release. Doxorubicin was labeled with 99mTc-DTPA and optimized to achieve high labeling efficiency. The in vitro stability was determined to check the efficiency of the system to establish the suitability of the radiolabeled system for in vivo studies. 99mTc-DTPA labeled doxorubicin bearing noncoupled and coupled liposomes was administered intravenously and biodistribution studies were performed. The distribution of doxorubicin via noncoupled and coupled liposomes was determined in various organs (i.e. lungs, liver, kidneys, spleen and brain) by measuring radioactivity using a gamma scintillation unit. An average 7-fold increased brain uptake of the drug was observed after liposomal delivery of doxorubicin, while the transferrin-coupled liposomes increased approximately 10 fold brain uptake of doxorubicin. We conclude that transferrin-coupled liposomes can enhance the brain uptake of drugs like doxorubicin.Vascular Disease Prevention 01/2007; 4(1):31-38. -
Article: Cross-linked guar gum microspheres: a viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer.
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ABSTRACT: In the present work, guar gum microspheres containing methotrexate (MTX) were prepared and characterized for local release of drug in the colon, which is a prerequisite for the effective treatment of colorectal cancer. Guar gum microspheres were prepared by the emulsification method using glutaraldehyde as a cross-linking agent. Surface morphological characteristics were investigated using scanning electron microscopy. Particle size, shape, and surface morphology were significantly affected by guar gum concentration, glutaraldehyde concentration, emulsifier concentration (Span 80), stirring rate, stirring time, and operating temperature. MTX-loaded microspheres demonstrated high entrapment efficiency (75.7%). The in vitro drug release was investigated using a US Pharmacopeia paddle type (type II) dissolution rate test apparatus in different media (phosphate-buffered saline [PBS], gastrointestinal fluid of different pH, and rat cecal content release medium), which was found to be affected by a change to the guar gum concentration and glutaraldehyde concentration. The drug release in PBS (pH 7.4) and simulated gastric fluids followed a similar pattern and had a similar release rate, while a significant increase in percent cumulative drug release (91.0%) was observed in the medium containing rat cecal content. In in vivo studies, guar gum microspheres delivered most of their drug load (79.0%) to the colon, whereas plain drug suspensions could deliver only 23% of their total dose to the target site. Guar gum microspheres showed adequate potential in achieving local release of drug in in vitro release studies, and this finding was further endorsed with in vivo studies.AAPS PharmSciTech 02/2006; 7(3):74. · 1.43 Impact Factor -
Article: Brain-Specific Delivery of Rifampin from Lactyl Stearate-Coupled Liposomes via Monocarboxylic Acid Transporters
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ABSTRACT: Background: The blood-brain barrier (BBB) is an obstacle for pharmacologists wishing to find treatments for patients with brain disorders. The BBB restricts the uptake of many valuable hydrophilic drugs and limits their efficacy because of the presence of tight junctions, a high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms.Aim: The present study aimed to characterize lactyl stearate-coupled liposomes and their potential for the brain targeting of rifampin (rifampicin).Method: A liposomal delivery system was prepared for achieving the brain-targeted delivery of rifampin in 21 albino rats utilizing the monocarboxylic acid transport system. Liposomes were prepared by the cast-film method using phosphatidylcholine and cholesterol. Similarly, lactyl stearate-coupled liposomal systems were prepared by casting lactyl stearate film with lipids. These liposomal formulations were characterized for entrapment efficiency, vesicle size, in vitro drug release (using dialysis membrane), and in vivo drug accumulation in various tissues.Results: Coupling of lactyl stearate to liposomes had a profound influence on entrapment efficiency. Entrapment efficiency was reduced from 41.28 ± 2.02% in uncoupled liposomes to 34.23 ± 1.60% in coupled liposomes. The vesicle size was increased after coupling with lactyl stearate. The in vitro drug release for the uncoupled formulation LIPO-3 was 62.9 ± 3.01% after 24 hours, whereas that of the coupled formulation LIPO-3-Ls-III was 44.5 ± 2.09%. The percentage of rifampin dose recovered from the brain following administration of lactyl stearate-coupled liposomes to albino rats at different time intervals was about 6–8 times higher than with uncoupled liposomes and about 10–12 times higher than with the plain drug solution.Conclusion: Lactyl stearate-coupled liposomes were better localized within the brain compared to uncoupled liposomes. Lactyl stearate-coupled liposomes could be an excellent carrier system for brain targeting of the hydrophilic drug rifampin.American Journal of Drug Delivery 12/2005; 4(1):43-49. -
Article: Glutamate-conjugated liposomes of dopamine hydrochloride for effective management of parkinsonism's.
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ABSTRACT: The blood-brain barrier restricts the brain uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, amino acid-coupled liposomes bearing dopamine HCl were prepared to deliver the drug to the brain utilizing receptor-mediated transcytosis. Uncoupled liposomes were prepared by cast film method using phosphatidylcholine and cholesterol, whereas coupled liposomes were prepared using phosphatidylcholine, cholesterol, and glutamate stearylamine conjugate in the film. These liposomes were characterized for entrapment efficiency, vesicle size, shape, in vitro drug release, and in vivo studies. The in vitro drug release was analysed by using dialysis membrane. The vesicle size was found to increase upon coupling of liposomes, whereas percent entrapment efficiency was reduced from 38.89 +/- 1.94% to 34.15 +/- 1.70% after coupling of liposomes. The in vitro percent cumulative drug release studies exhibited 51.6% drug release for uncoupled liposome and 37.9% for coupled liposome at the end of 24 h. These selected formulations were subjected for in vivo performance, which was assessed by periodic measurement of drug (chlorpromazine)-induced catatonia in albino rats (Wistar strain) and fluorescence microscopy studies of the rat brain. The results were compared with plain dopamine HCl solution. Studies revealed that dopamine HCl can be effectively delivered to brain via glutamate-coupled liposomes, and results clearly indicated the superiority of the coupled liposomal formulation over the uncoupled formulation.PDA journal of pharmaceutical science and technology / PDA 63(5):372-9.
