Sustained release of proteins from a modified vaginal ring device

A new vaginal ring technology, the insert vaginal ring (InVR), is presented. The InVR overcomes the current shortfall of conventional vaginal rings (VRs) that are generally ineffectual for the delivery of hydrophilic and/or macromolecular actives, including peptides, proteins and antibodies, due to their poor permeation characteristics in the hydrophobic polymeric elastomers from which VRs are usually fabricated. Release of the model protein BSA from a variety of insert matrices for the InVR is demonstrated, including modified silicone rods, directly compressed tablets and lyophilised gels, which collectively provided controlled release profiles from several hours to beyond 4 weeks. Furthermore, the InVR was shown to deliver over 1 mg of the monoclonal antibody 2F5 from a single device, offering a potential means of protecting women against the transmission of HIV.

Comparative validation of c-kit exon 11 mutation analysis on cytology samples and corresponding surgical resections of gastrointestinal stromal tumours

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Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

RF performance of a 418-MHz radio telemeter packaged for human vaginal placement

The electrical and communication performance of a 0.8-mu W UHF temperature telemeter designed for human vaginal placement is discussed; a solenoidal loop antenna was used, occupying a volume of 0.1 cm(3). In situ, measured power absorption was between 19-25 dB, resulting in an effective operating range of 10 m. Capacitive loading lowered the antenna's resonant frequency by 1.4% and there was a significant polarization change in the radiated output.

Vaginal temperature sensing using UHF radio telemetry

User induced errors are common when women repetitively employ conventional probe type thermometers to chart their basal body temperatures in an effort to indicate ovulation. An alternative technique employing a two-part telemetric thermometer is proposed, with low-power, SAWR-controlled UHF radio as the transmission medium. Worn overnight in the vagina, the 1 mu W erp telemetry transmitter sends pulse modulated data continuously to a microcontroller in a nearby receiver; a real time clock enables programmable sampling and storage of the subject's temperature to 0.1 degrees C resolution. Initial clinical results indicate an enhanced performance compared to oral and axillary temperature trends taken by a mercury-in-glass thermometer. Polar plots of both the isolated and body-worn telemetry transmitte are presented; body indced attenuations of up to 30 dB were measured.