Sustained release strategies for HIV microbicides and vaccines

• Main Author: Lowry, Deborah
• Published: Queen's University Belfast 2007
• Subjects: 615.19
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486247

Human immunodeficiency virus (HIV) lolls more people worldwide than' any other infectious disease. The main mode of transmission of HN is unprotected heterose~al intercourse with an infected partner. There is a need for the development of female controlfed preventative strategies. the most promising approach currently being pursued is the development of vaginally administeled HN. microbicides. The release profiles from silicone intravaginal rings (lVRs) of (i) potential HN fusion inhibitors. dextran sulfate (OS) and ceJJuJose sulfate (CS). (ii) organic acid species, and .(iii) bovine serum albumin (BSA) was inveStigated. An assay using high performance liquid chromatography (HPlC) in conjunction with the evaporative light scattering detector (ELSO) for OS was developed. OS of two molecular weights and CS demorlSbated sustained and continuous release from matrix, reservoir and perforated (4 and 8 holes) type IVRs. The presence of bovine serum alblmin resulted in an enhanced reJease profile for OS. The~of OS also resulted in enhanced release of metronidazole from the fVRs. The CS release profiles from the IVRs produced concentrations that may be maintained at clinically optimised levels for prevention of HN. The organic acid release demonstrated proof of concept for sustained release and lowering the pH of the release medium. The BSA release from the IVRs was enhanced by the presence of OS (200h wlw). Further sustained and continuoUs release of tiny amounts of BSA has been demonstrated from covered sirlCOOe rod fonnulations. OS present in the rods (10% _ 50% wlw) enhanced the release of BSA. This study provides further evidence that may have major implications for the design of a sustained release system for vaginal immunization against HN.