Preparation and Evaluation of Paclitaxel-Loaded Albumin Nanoparticles Containing Thermo-Sensitive Hydrogel

The development of long-acting drug preparations is a crucial strategy for enhancing the safety, efficacy, and patient compliance of clinical treatments for certain diseases. In the field of oncology, the world’s first long-acting anti-tumor microsphere formulation (Lupron Depot®) was approved in the United States as early as the 1980s. However, microsphere formulations suffer from drawbacks such as complex manufacturing processes, challenging quality control, and stringent storage requirements. To address these limitations, this study aimed to develop a novel intranasal injectable thermosensitive gel formulation loaded with albumin-bound paclitaxel nanoparticles (BSA-PTX NPs) and characterize it in vitro. We first optimized the BSA-PTX NP formulation using single-factor experiments followed by Box-Behnken response surface methodology. The optimized nanoparticles exhibited a particle size range of 95.85 - 181.25 nm, an encapsulation efficiency of 47.67% - 96.73%, and a drug loading capacity ranging from 4.33% to 8.79%. Subsequently, Poloxamer was selected as the gel matrix, and the optimal excipient concentrations were determined. Finally, the influence of BSA-PTX NPs loading on the gel’s phase transition temperature was investigated, and drug release studies were conducted. The results demonstrate that the Poloxamer-based thermosensitive gel loaded with BSA-PTX NPs is simple to prepare, exhibits excellent injectability, and possesses a body temperature-responsive phase transition temperature. This formulation represents a promising in-situ forming, long-acting anti-tumor drug delivery system. The optimized thermosensitive hydrogel was composed of 18% Poloxamer 407, 0.1% Poloxamer 188, and 0.5% hyaluronic acid, with a phase transition temperature of 32.1˚C ± 0.1˚C. In vitro drug release studies showed that over 80% of paclitaxel was released within 48 h in pH 5.5 buffer, exhibiting a sustained release profile.