HIV’s drug formulations for long-term refillable subcutaneous drug release device.

HIV (Human Immunodeficiency Virus) is a retrovirus that debilitates the immune system. In 2023, an estimated 39.9 million individuals live with HIV, with 1.3 million new infections and 630,000 AIDS-related passings. Without treatment, HIV advances to AIDS (Acquired Immunodeficiency Syndrome), severely impairing immunity. Early diagnosis and consistent treatment are pivotal. Antiretroviral therapy (ART) is the cornerstone of HIV treatment. ART reduces viral loads to undetectable levels, preventing progression and transmission. However, ART requires strict daily adherence to avoid drug resistance, presenting a major challenge for long-term treatment consistency. To overcome this, a subcutaneous implantable device (NanoDDI) enables continuous drug release for at least two years from a single hand injection. It consists of a drug reservoir, a porous nanochannel membrane, a titanium filter, and two self-sealing silicon rubber ports. Interstitial fluids permeate the nanochannels, dissolving the drug, which is at that point released by diffusion, with the release rate controlled by the size and number of channels. This study aims to create an optimal formulation of a new antiretroviral drug to address compaction during device refilling. While some drug is initially released, the remaining drug becomes compacted inside the device, especially around the filter, preventing further sustained release over time. To address this, different excipients, commonly used as anticaking agents, and different mixing approaches were employed to improve drug solubility and prevent aggregation. Diverse testing devices were developed to evaluate these formulations, pointing to replicate as closely as possible the characteristics of the device designed for in vivo and in vitro studies, thereby simulating realistic conditions. This approach offers the added benefit of being easy to assemble and reassemble, making the testing process more efficient and reproducible. The most promising formulations were first selected through qualitative analyses, and then evaluated with quantitative tests that measured drug accumulation inside the device and the force required for injection. The device was filled using a syringe pump to maintain a steady flow rate and was tested at different time points, with the goal of completing the refill in under one minute with a single injection. Results showed that sugars are promising excipients. An ongoing in vitro study is evaluating long-term release profiles using trehalose-based formulations and varying drug loads to clarify how formulation and loading influence implant performance. Sugar-based formulations have shown promising results in terms of drug release. However, longer observation times are required to evaluate their long-term stability and performance. Ongoing studies will confirm their potential for long-term HIV treatment with NanoDDI and in vivo studies are planned.