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02665 IN VITRO RELEASE OF DEXTRAN SULFATE FROM SILICONE INTRAVAGINAL RINGS MALCOLM, KARL Dextran sulphate is a polymeric species containing a negatively charged glycoprotein surface which potently inhibits the absorption of HIV to CD4+ cells by binding to the neutralising domains of gp120. It is currently being evaluated in vaginal microbicidal gel formulations for the prevention of heterosexual transmission of HIV. However, from the perspective of providing long-term, female-friendly, patient-compliant, continuous protection against HIV transmission, microbicides incorporated into vaginal gel formulations are far from ideal. For example, the retention of gels (and thus the microbicidal substance) within the vagina is poor, they are messy and difficult to adminster, there is the need for gel application before every act of intercourse, and the nature of a gel is such that it is unlikely be used without the knowledge of the male partner. Silicone intravaginal rings (IVRs) are controlled release drug delivery devices that have been specifically designed to overcome the numerous disadvantages associated with gel formulations. In this study, dextran sulfate (weight average molecular weight 5000 and 10,000 daltons) has been incorporated into various matrix-type and reservoir-type IVR formulations and the in vitro release characteristics (employing an aqueous dissolution medium) evaluated using HPLC in conjunction with an evaporative light scattering detector (ELSD). The results demonstrate that dextran sulfate may be released in milligram quantities per day, dependent upon molecular weight and loading. DR. KARL MALCOLM |
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