No abstract

Polymer solutions can fill any potential irregular cavity using minimally invasive techniques and thus have potential uses in ophthalmology. We prepared acrylamide hydrogels containing disulfide bonds by free radical polymerization in aqueous ethanol. The hydrogels were liquefied using dithiothreitol to yield water-soluble acrylamide copolymers containing pendant thiol (-SH) groups. The weight average molecular weights of the copolymers ranged from 1.43 x 10(5) to 9.22 x 10(5) daltons by GPC. Ellman's analysis and Raman spectroscopy confirmed the presence of -SH. The aqueous solutions of these purified thiol-containing copolymers were oxidized with 3,3'-dithiodipropionic acid or air to reform the hydrogels. The moduli of the reformed hydrogels ranged from 0.27 to 1.1 kPa depending on concentration and thiol content. Rapid endocapsular gelation yielded optically clear gel within the lens capsular bag. This technique now enables us to validate methods to determine the biomechanics of the lens and its role in accommodation.

Silicones have been used in medicines, cosmetics and medical devices for over 60 years. Polydimethylsiloxanes are polymers that are typically used either as an active in oral drug products or as excipients in topical and transdermal drug products. Inherent characteristics like hydrophobicity, adhesion and aesthetics allow silicones to offer function and performance to drug products. Recent technologies like swollen crosslinked silicone elastomer blend networks, sugar siloxanes, amphiphilic resin linear polymers and silicone hybrid pressure sensitive adhesives promise potential performance advantages and improved drug delivery efficacy. This article presents a review of recent silicone material developments focusing on their function as excipients influencing drug delivery in topical and transdermal systems.

We describe the engineering of a degradable intravaginal ring (IVR) for the delivery of the potent HIV-1 reverse transcriptase inhibitor dapivirine. The degradable polymer used in fabricating the device incorporated poly(caprolactone) ester blocks in a poly(tetramethylene ether) glycol ABA type polyurethane backbone. The polymer was designed to maintain its structure for 1 month during usage and then degrade in the environment post-disposal. In vitro release of dapivirine showed zero-order kinetics for up to 1 month and significant levels of drug release into engineered vaginal tissue. The mechanical properties of the degradable IVR were comparable to those of a widely used contraceptive intravaginal ring upon exposure to simulated vaginal conditions. Incubation under simulated vaginal conditions for a month caused minimal degradation with minimal effect on the mechanical properties of the ring and polymer. The cytotoxicity evaluation of the drug-loaded IVRs against Vk2/E6E7 human vaginal epithelial cells, Lactobacillus jensenii, and engineered vaginal tissue constructs showed the degradable polyurethane to be non-toxic. In vitro evaluation of inflammatory potential monitored through the levels of inflammatory cytokines IL-8, IL-1α, IL-6, IL-1β, and MIP-3α when engineered EpiVaginal™ tissue was incubated with the polyurethanes suggested that the degradable polyurethane was comparable to commercial medical grade polyurethane. These results are encouraging for further development of this degradable IVR for topical vaginal delivery of microbicides.