The Effect of Tacticity on the Conformational Properties of Poly(1-olefin sulfone)s

The effect of tacticity on the conformational properties of poly(olefin sulfone)s was studied. Tactic polymers, prepared from racemic thiirane monomers using chiral inititators were compared with atactic polymers prepared by free radical co-polymerisation of the 1-olefin with sulfur dioxide. Analysis of the XRD patterns showed that the tactic polymers formed more ordered structures in the bulk with longer layer spacings, consistent with a model in which their side chains meet at the tips in contrast with the atactic polymers whose side chains interdigitate. 13C MAS nmr experiments suggest that as tacticity increases so too does the proportion of C-S bonds in the gauche conformation, however the proportion of S-C bonds in the trans conformation falls, in contrast to a reported molecular mechanics study. Finally, DSC measurements on the polymers with longer side chains showed the presence of two endotherms on heating, illustrating definite liquid crystalline behaviour.

Safety and Pharmacokinetics of Dapivirine Delivery From Matrix and Reservoir Intravaginal Rings to HIV-Negative Women

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twentyfour
healthy HIV-negative women 18–35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma
and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were ,2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.

In vitro release of dextran sulfate from silicone intravaginal rings

Abstract 02665