Screening Ganoderma Lucidum Spore Oil-based Oral Solid Self-microemulsion of Paclitaxel for Enhanced Chemotherapeutic Efficacy via Immunomodulation in Colorectal Cancer

Solid self-microemulsifying drug delivery systems (SMEDDS) offer unique advantages over conventional liquid formulations, including enhanced physical stability, simplified storage/transportation, and improved drug delivery efficiency. In this study, we developed a paclitaxel (PTX)-loaded SMEDDS using Ganoderma lucidum spore oil (GLSO) as a multifunctional oil phase. Through formulation screening and optimization, the PTX-GLSO-SMEDDS was successfully converted into a solid powder. Solid-state analyses confirmed the amorphous dispersion of PTX within the matrix, while the powder exhibited favorable fluidity, stability, and rapid in vitro drug release kinetics. PTX-GLSO-SMEDDS demonstrated potent antitumor effects by inducing apoptosis and suppressing metastasis in colorectal cancer (CRC) cells. In vivo studies revealed dual therapeutic advantages: enhanced tumor suppression and synergistic immunomodulation via GLSO-mediated activation of tumor-associated cytotoxic T lymphocytes regulation. Notably, the formulation reduced systemic toxicity compared to conventional PTX injections. By integrating GLSO's inherent bioactivity with SMEDDS technology, this work establishes a robust platform that synergizes chemotherapy and immunotherapy, offering a clinically translatable strategy for CRC treatment with improved safety and therapeutical outcomes. The findings underscore GLSO's potential as a natural, multifunctional excipient for advanced drug delivery systems.