Title:
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Sustained release strategies for HIV microbicides and vaccines
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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.
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