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A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113µg while Day 60 values ranged from 284 to 454µg. Daily LNG release ranged from 129 to 684µg on Day 1 and 2-91µg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131µg/day or 37-66µg/day for DPV, and either 96-150µg/day or 37-57µg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.

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Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control.

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Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine - a lead candidate antiretroviral microbicide - for combination HIV prevention and hormonal contraception.

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We report a plasmonic paper-based analytical platform with functional versatility and subattomolar (<10(-18) M) detection limit using surface-enhanced Raman scattering as a transduction method. The microfluidic paper-based analytical device (µPAD) is made with a lithography-free process by a simple cut and drop method. Complex samples are separated by a surface chemical gradient created by differential polyelectrolyte coating of the paper. The µPAD with a starlike shape is designed to enable liquid handling by lateral flow without microchannel patterning. This design generates a rapid capillary-driven flow capable of dragging liquid samples as well as gold nanorods into a single cellulose microfiber, thereby providing an extremely preconcentrated and optically active detection spot.

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The mechanism by which small molecules assemble into microscale tubular structures in aqueous solution remains poorly understood, particularly when the initial building blocks are non-amphiphilic molecules and no surfactant is used. It is here shown how a subnanometric molecule, namely p-aminothiophenol (p-ATP), prepared in normal water with a small amount of ethanol, spontaneously assembles into a new class of nanovesicle. Due to Brownian motion, these nanostructures rapidly grow into micrometric vesicles and start budding to yield macroscale tubular branches with a remarkable growth rate of ∼20 µm s⁻¹. A real-time visualization by optical microscopy reveals that tubular growth proceeds by vesicle walk and fusion on the apex (growth cone) and sides of the branches and ultimately leads to the generation of centimeter-long microtubes. This unprecedented growth mechanism is triggered by a pH-activated proton switch and maintained by hydrogen bonding. The vesicle fusion-mediated synthesis suggests that functional microtubes with biological properties can be efficiently prepared with a mixture of appropriate diaminophenyl blocks and the desired macromolecule. The reversibility, timescale, and very high yield (90%) of this synthetic approach make it a valuable model for the investigation of hierarchical and structural transition between organized assemblies with different size scales and morphologies.