title: Modified Release Biodegradable Polymeric Microspheres of Stavudine: Cell Viability, Cellular Uptake, Hemolysis Studies and In Vivo Pharmacokinetics.
abstract: Family of retroviruses which replicates through the use of the reverse transcriptase enzyme or the enzyme needed to convert RNA to DNA for replication bears Human Immunodeficiency Virus (HIV). It causes irreversible destruction of the immune system leading to the occurrence of opportunistic infections and malignancies. The eradication of HIV is highly unlikely as the cells of the mononuclear phagocyte system (MPS) besides CD4 T lymphocytes are the specific hosts for HIV which need to be targeted even after extended blood plasma profile of antiviral drug to maintain viral suppression and reduced disease progression. Aiming the current goal, biodegradable polymeric microspheres of PLGA 50: 50 (RESOMER(®) 505H) were developed and evaluated. These polymeric particles encapsulating Stavudine (d4T) exhibited nearly 100% cell viability during cytotoxicity studies in comparison to pure d4T. The histological studies have revealed the in vivo biocompatibility while hemolysis studies certified the liability of formulation to be used parenteraly exhibiting no significant hemolytic toxixicty. The in vivo pharmacokinetics has shown the extended drug release from microsphere matrix upto a month. The calculated AUCtotal for d4T loaded polymeric microspheres was found to be 3341.656 μM h/ml; which was nearly 54 times than the total AUC of free d4T injected subcutaneously to the control group of animals; exhibiting the stable d4T concentration in blood avoiding fluctuation of the same indicating decreased probabilities of development of resistance against the treatment. Combination of targeted and subcutaneous administration of d4T will not only provide the stable and extended release of drug but also eradicate the hidden HIV hosted by macrophages. The concomitant regimen will potentially enhance the therapeutic efficacy with patient compliance; renewing new hopes for complete cure and improved quality of life in the AIDS patient.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Srivastava
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kumar
authors.forename: S K
authors.initials: SK
authors.lastname: Arora
authors.affiliation: Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh -160014, India. sinha_vr@rediffmail.com.
authors.forename: V R
authors.initials: VR
authors.lastname: Sinha
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D063566:Biodegradable Plastics / Q000378:metabolism; D001774:Blood Chemical Analysis; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D007279:Injections, Subcutaneous; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008863:Microspheres; D051381:Rats; D018119:Stavudine / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D063566:Biodegradable Plastics; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D018119:Stavudine