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.

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Summary Acid stimulation, for both oil and gas wells, greatly supports the industry as a versatile means of enhancing production. Although acids enhance carbonate reservoir permeability to hydrocarbons, the reaction rates of the acid [e.g., hydrochloric acid (HCl)] with the rock often are too rapid at high temperatures, leading to a reduction in acid penetration. Several methods exist to improve the effectiveness of acidizing in high-temperature reservoirs (e.g., greater than 120°C), including the use of conventional emulsified-acid systems, mixtures of HCl and organic acids, and gelled acids. Many of the aforementioned techniques are effective forms of treatment; however, they hold significant limitations such as reduction in acid efficiency, poor control over penetration depth, and the requirement of corrosion inhibitors. Accordingly, encapsulated HCl holds potential as an attractive alternative to address these shortcomings because its prolonged release profile would permit transport of acid deep within the reservoir. In addition, when successfully encapsulated, this technology could eliminate, or at the very least minimize, the use of corrosion inhibitors. Herein, we demonstrate the design and preparation of highly modular core/shell particles comprising concentrated HCl encapsulated within an acrylate-based thermoset polymer shell. We show that the shell-generation mechanism (i.e., photopolymerization of acrylate monomers) is compatible with concentrated HCl and further detail the encapsulation process. Our results demonstrate that the acid-release profiles are dictated by the properties of the shell material, enabling a prolonged delivery of HCl in laboratory studies. This is a first step toward the design of particle-shell systems that can tolerate harsh reservoir conditions, including high temperatures, pressures, and salinity of mixing water. A tunable core/shell delivery system that encompasses a sufficient amount of strong mineral acid is well-poised to address the unmet need of deeper penetration of HCl into the reservoir, enabling greater stimulation efficiency.

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Acid stimulation, for both oil and gas wells, greatly supports the industry as a versatile means of enhancing production. Although acids enhance carbonate reservoir permeability to hydrocarbons, the reactions rates of the acid (e.g., HCl) with the rock often occur too rapidly at high temperatures, leading to a reduction in acid penetration. Several methods exist to improve the effectiveness of acidizing in high temperature reservoirs (i.e., greater than 250°F), including the use of emulsified acid, mixtures of hydrochloric acid (HCl) and organic acids, and gelled acids. Many of the aforementioned techniques are effective forms of treatment; however, they hold significant limitations such as reduction in acid efficiency, poor control over penetration depth and the requirement of corrosion inhibitors. Acc ordingly, encapsulated HCl holds potential as an attractive alternative to address these shortcomings since its prolonged release profile would permit transport of acid deep within the reservoir. In addition, when successfully encapsulated, this technology could completely eliminate the use of corrosion inhibitors. Herein, we demonstrate the design and preparation of highly modular core-shell particles comprising concentrated HCl encapsulated within an acrylate-based thermoset polymer shell. We show that the shell generation mechanism (i.e., photopolymerization of acrylate monomers) is compatible with concentrated HCl and further detail the encapsulation process. Our results demonstrate that acid release profiles are dictated by the properties of the shell material, enabling a prolonged delivery of HCl in laboratory studies. This is a first step towards the design of particle shell systems that can tolerate the harsh reservoir conditions, including high temperatures, pressures, and salinity of mixing water. A tunable core-shell delivery system that encompasses a sufficient amount of strong mineral acid is well-poised to address the unmet need of deeper penetration of HCl into the reservoir enabling greater stimulation efficiency.