Antiretrovirals: Need for an effective drug delivery

Abstract

Human Immunodeficiency Virus (HIV) is a retrovirus that causes irreversible destruction of the immune system, leading to the occurrence of opportunistic infections and malignancies. During the last decade, even though attempts were being made to eradicate HIV, it was found that eradication of HIV is highly unlikely, and effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression. During this decade, effective therapies aimed at continued suppression of HIV replication and targeted at resting HIV reservoirs such as brain, lymphatic systems will be critical to prolong survival and renewing hopes for a cure. Currently available antiHIV drugs can be classified into three categories: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Most of these drugs bear some significant drawbacks such as relatively short half-life, low bioavailability, poor permeability and undesirable side effects. Efforts have been made to design drug delivery systems for antiHIV agents to: a) reduce the dosing frequency, b) increase the bioavailability and decrease the degradation/metabolism in the gastrointestinal tract, c) improve the CNS penetration and inhibit the CNS efflux, and d) deliver them to the target cells selectively with minimal side effects. This article is an attempt to compile all major research work towards drug delivery for AIDS therapy and channel future attempts in the area of more effective controlled delivery of antiHIV agents.

An Introduction to the Approaches of Novel Drug Delivery Systems for Acquired Immune Deficiency Syndrome (AIDS)

“…There is currently no vaccine or cure for HIV or AIDS. Therapy is based on avoiding exposure to the virus or an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP) [4]. The major classes of antiretroviral agents are as follows:…”

Atazanavir-loaded Eudragit RL 100 nanoparticles to improve oral bioavailability: optimization andin vitro/in vivoappraisal

“…It has been well reported in the literature that daily dose of ATV causes serious liver problems, specifically hepatotoxicity (Devi & Pai, 2006). As a shortfall for all the conventional oral dosage forms, the duration of action is limited since the absorption of the drug depends on the resident time of the drug in the gastrointestinal tract.…”

Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations

“…Nevirapine (NVP) is an orally active antiretroviral drug approved by FDA that is currently used in the treatment of human immunodeficiency virus type 1 (HIV-1) infections (Devi & Pai, 2006;Waters et al, 2007), is particularly insoluble in water at physiological pH conditions and soluble only under extremely acidic media (Merck Index, 2006). NVP belongs to Biopharmaceutical Classification System (BCS) class II (low solubility/high permeability), poses a challenge in achievement of optimal dissolution kinetics from the dosage form (Kasim et al, 2004).…”