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The development of a long-acting injectable drug delivery systems (DDS) of active pharmaceutical ingredients (API) holds great promise in addressing the challenges of treatment adherence, predominantly in HIV/AIDS. Polymers are inevitable carriers for the preparation of DDS, which are typically composed of polylactide (PLA), carbohydrates such as chitosan or cellulose derivatives. In this study, the tenofovir alafenamide (TAF) laden PLA-stereocomplex-chitosan nanoparticles (Sc-PLA-chitosan NPs) were developed through the spray-dried technique. These NPs had a mean particle size of 91 ± 8 nm and were incorporated into oleogels consisting of sesame oil and ethyl-cellulose. To enhance the syringeability of highly viscous oleogels, the commercially available aluminium oxide NPs were added with a size of 78 nm. The proposed DDS exhibits prolonged sustained release for up to 12 days in phosphate buffer pH 7.4. Noteworthy, the oleogels with Sc-PLA-chitosan NPs displayed extended tissue permeation properties indicating their potential long-acting in-vivo drug release. Collectively, this study recommends that the development of Sc-PLA-chitosan NPs-loaded oleogels represents a certainly adaptable long-acting injectables system for the delivery of APIs in the context of HIV/AIDS. This system is expected to contribute to improved and effective treatment adherence among patients infected with HIV and provide requisite therapeutic outcomes., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of suitable drug delivery systems for prolonged action against HIV receives great attention in recent research. Herein, a long-acting injectable (LAI) of Tenofovir alafenamide-chitosan polymeric nanoparticles loaded oleogels developed with sesame oil and ethyl cellulose for prolonged release of the drug is reported for the first time. The research resulted with unique long-acting parenteral formulation for chronic anti-retroviral therapy, based on our experimental in-vitro and ex-vivo studies. The chitosan nanoparticles with 49 % drug content were produced through the spray-drying technique and characterized for their size (106-540 nm) and the other physico-chemical features through SEM, FT-IR, XRD, TGA, and DSC. The ethyl cellulose and sesame oil oleogels were developed through a heat-cool process by incorporating the drug-loaded chitosan nanoparticles. The oleogels exhibited extended release (56 %) of the drug for 16 days, which could be prolonged further to achieve the maximum drug release. Also, the ex-vivo permeation studies of the nanoparticles loaded oleogels demonstrated about 10-fold decrease in the flux and the permeation of the drug due to prolonged release of the drug across dual barriers of chitosan nanoparticles and ethyl cellulose gel matrix. The result provided proof-of-evidence that the developed Tenofovir alafenamide-chitosan polymeric nanoparticles loaded with ethyl cellulose oleogels could be potentially used as the long-acting injectable system for the treatment of patients infected with HIV/AIDS., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)