Abstract
The present study is aimed at evaluating the transdermal route as an alternative to the oral route for improving the systemic bioavailability and sustaining the constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal formulations of AZT were prepared and characterized. The effect of different formulation variables on transdermal delivery of AZT from elastic liposomes was studied. To investigate the mechanism of skin permeation of elastic liposomes, Transmission Electron Microscopic (TEM) study was carried out. The optimized elastic liposomal formulation showed transdermal flux of 98.8 ± 5.8 μg/cm2/hr across rat skin as compared to 5.72 ± 0.3 μg/cm2/hr for free drug. Vesicle-skin interaction study showed that elastic vesicles influenced the ultra structure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular spaces of the stratum corneum. These stacks disrupted the organization of skin bilayers leading to increased skin permeability, whereas no changes were observed in the underlying viable epidermis and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to be (12.63±1.2 μg h/mL), nearly twelve fold higher than the control (0.83±0.2 μg h/mL). Furthermore, the administration of elastic liposome encapsulated AZT resulted in substantially higher accumulation of AZT in target RES organs that play a key role in the pathogenesis of AIDS by providing long-term reservoir for the virus. The results of the present study demonstrated that elastic liposomes increased the transdermal flux, prolonged the release, improved the site specificity of AZT and represented an attractive strategy for sustained and targeted delivery of AZT.
Keywords: Zidovudine, transdermal, elastic liposomes, penetration enhancer, transmission electron microscopy, mechanism
Current Drug Delivery
Title: Sustained and Targeted Delivery of an Anti-HIV Agent Using Elastic Liposomal Formulation: Mechanism of Action
Volume: 3 Issue: 2
Author(s): Subheet Jain, A. K. Tiwary and N. K. Jain
Affiliation:
Keywords: Zidovudine, transdermal, elastic liposomes, penetration enhancer, transmission electron microscopy, mechanism
Abstract: The present study is aimed at evaluating the transdermal route as an alternative to the oral route for improving the systemic bioavailability and sustaining the constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal formulations of AZT were prepared and characterized. The effect of different formulation variables on transdermal delivery of AZT from elastic liposomes was studied. To investigate the mechanism of skin permeation of elastic liposomes, Transmission Electron Microscopic (TEM) study was carried out. The optimized elastic liposomal formulation showed transdermal flux of 98.8 ± 5.8 μg/cm2/hr across rat skin as compared to 5.72 ± 0.3 μg/cm2/hr for free drug. Vesicle-skin interaction study showed that elastic vesicles influenced the ultra structure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular spaces of the stratum corneum. These stacks disrupted the organization of skin bilayers leading to increased skin permeability, whereas no changes were observed in the underlying viable epidermis and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to be (12.63±1.2 μg h/mL), nearly twelve fold higher than the control (0.83±0.2 μg h/mL). Furthermore, the administration of elastic liposome encapsulated AZT resulted in substantially higher accumulation of AZT in target RES organs that play a key role in the pathogenesis of AIDS by providing long-term reservoir for the virus. The results of the present study demonstrated that elastic liposomes increased the transdermal flux, prolonged the release, improved the site specificity of AZT and represented an attractive strategy for sustained and targeted delivery of AZT.
Export Options
About this article
Cite this article as:
Jain Subheet, Tiwary K. A. and Jain K. N., Sustained and Targeted Delivery of an Anti-HIV Agent Using Elastic Liposomal Formulation: Mechanism of Action, Current Drug Delivery 2006; 3 (2) . https://dx.doi.org/10.2174/156720106776359221
DOI https://dx.doi.org/10.2174/156720106776359221 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Altered Steroid Metabolism and Insulin Signaling in PCOS Endometria: Impact in Tissue Function
Current Pharmaceutical Design Insulin Delivery Systems for Controlling Diabetes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery TRPM Channels Phosphorylation as a Potential Bridge Between Old Signals and Novel Regulatory Mechanisms of Insulin Secretion
Current Diabetes Reviews Global Cell Proteome Profiling, Phospho-signaling and Quantitative Proteomics for Identification of New Biomarkers in Acute Myeloid Leukemia Patients
Current Pharmaceutical Biotechnology A Common Pathway for All Autoimmune Diseases? The Unholy Alliance of Environment, Cell Death and Nucleic Acids
Current Immunology Reviews (Discontinued) Pharmacological Applications of Antioxidants: Lights and Shadows
Current Drug Targets Presentation of Lipid Antigens by CD1 Glycoproteins
Current Pharmaceutical Design Hematological Targets of Radiation Damage
Current Drug Targets Mechanisms Used by Human Papillomaviruses to Escape the Host Immune Response
Current Cancer Drug Targets Herb-Drug Interactions and Mechanistic and Clinical Considerations
Current Drug Metabolism Platelet-Monocyte Interactions - A Dangerous Liaison Linking Thrombosis, Inflammation and Atherosclerosis
Current Medicinal Chemistry Role of Androgens in Womens Sexual Function & Dysfunction: What Have We Learned in Six Decades?
Current Women`s Health Reviews Role of Iodine, Selenium and Other Micronutrients in Thyroid Function and Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets HIV-1 Neutralization: Mechanisms and Relevance to Vaccine Design
Current HIV Research Mitochondrial Dysfunction and Antioxidant Therapy in Sepsis
Infectious Disorders - Drug Targets Role of Fibroblast Growth Factor 21 (FGF21) in the Regulation of Statural Growth
Current Pediatric Reviews Therapeutic Modulation of Coagulation and Fibrinolysis in Acute Lung Injury and the Acute Respiratory Distress Syndrome
Current Pharmaceutical Biotechnology Targeting the Arrhythmogenic Substrate in Atrial Fibrillation: Focus on Structural Remodeling
Current Drug Targets Involvement of the Apoer2 and Lrp1 receptors in mediating the pathological effects of ApoE4 in vivo
Current Alzheimer Research Parkinson’s Disease and Alpha-Synucleinopathies: from Arising Pathways to Therapeutic Challenge
Central Nervous System Agents in Medicinal Chemistry