Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by long acting drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5–4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at < 2.8mg/day. Prototype devices demonstrated linear release at 1.2mg/day for up to 90 days and at 2.2mg/day for up to 60 days. Conclusions We present a biodegradable TFPD for subcutaneous delivery of TAF for HIV PrEP. The size, shape and release rate of the device are tunable over a > 8-fold range.

Herein, we present a novel approach for the fabrication of micropatterned polymeric nanowire arrays that addresses the current need for scalable and customizable polymer nanofabrication. We describe two variations of this approach for the patterning of nanowire arrays on either flat polymeric films or discrete polymeric microstructures and go on to investigate biological applications for the resulting polymeric features. We demonstrate that the micropatterned arrays of densely packed nanowires facilitate rapid, low-waste drug and reagent localization with micron-scale resolution as a result of their high wettability. We also show that micropatterned nanowire arrays provide hierarchical cellular control by simultaneously directing cell shape on the micron scale and influencing focal adhesion formation on the nanoscale. This nanofabrication approach has potential applications in scaffold-based cellular control, biological assay miniaturization, and biomedical microdevice technology.

Purpose To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs’ physicochemical properties. Methods Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis. Results Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with logP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models. Conclusion The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems.