Pla Stereocomplex-Chitosan Nanoparticles Loaded Oleogels as Long-Acting Injectable Drug Delivery System of the Anti-Hiv Drug Tenofovir Alafenamide

Abstract

The non-adherence to anti-HIV treatment seems to be a more formidable obstacle to HIV-free generation, due to multiple regimens. To overcome the limitations, Long-acting injectable (LAI) formulations for HIV treatment have been introduced in the market recently. The study aims to develop a PLA stereocomplex nanoparticles-based injectable oleogel system of Tenofovir Alafenamide for long-acting therapy of HIV-infected patients. The nanoparticles produced by the spray-drying technique exhibited particle sizes of 150-500 nm and SEM analysis confirm the particles as smooth and spherical. The functional groups observed in FTIR analysis revealed the existence and stability of the drug in nanoparticles. Thermo-gravimetric and differential scanning calorimetry (TG-DSC) analysis of nanoparticles showed a shift in the endothermic peak of the drug compared to the pure drug melting at 210 oC, which confirmed the solid-state transition of a drug in the presence of polymer. X-Ray Diffraction (XRD) pattern confirmed the polymorphic change of crystalline drug into semi-crystalline form during nanoparticle formation. Further, the optimized formulation of nanoparticles was incorporated into the ethyl cellulose (EC)-sesame oil oleogels and characterized for physicochemical properties. The microscopy analysis confirms the 3D network structure of EC in sesame oil, whereas, their viscosity is in the range of 9991-17250 (cP) at the lower shear rate (rpm). The pH of the oleogels and surrounding fluid is 7.4 and the syringeability is found suitable for LAI. The FTIR, TGA, and DSC analysis confirm the stability of the drug in oleogel formulations loaded with TAF pure drug and nanoparticles. In addition, the formulations were subjected to in-vitro drug release studies and the optimized nanoparticles loaded oleogel formulations demonstrated sustained drug release for 2 weeks. The solid-like gel would form a depot at the injection site, thereby releasing the medicaments slowly for a prolonged time and also helping to improve patient compliance.