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Development of Surfactant-Modified Liposomal Lomustine to Improve Blood-Brain Barrier Transport and Therapeutic
Kamonlatth Rodponthukwaji1,2, Natsuda Kunwong1,2, Pucharee Songprakhon3
1Siriraj Center of Research Excellence in Theranostic Nanomedicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Abstract:
Effective chemotherapy for glioma remains limited by the restrictive nature of the blood-brain barrier (BBB). In this work, a pH-responsive polysorbate 80-coated liposomal nanocarrier loaded with lomustine (CCNU@T80-LIP) was developed to enhance the delivery and therapeutic efficacy of lomustine (CCNU) against glioma. The liposomes exhibited spherical morphology, uniform size distribution, and high encapsulation efficiency. The formulation demonstrated pH-triggered drug release under acidic conditions, supporting its potential for endosomal escape and controlled intracellular delivery. In vitro studies revealed that CCNU@T80-LIP exhibited strong, dose-dependent cytotoxicity against U87-MG glioma cells while maintaining minimal toxicity toward hCMEC/D3 endothelial cells. In 3D tumor spheroids, the formulation achieved enhanced penetration and reduced cell viability to 76.81 ± 14.29%, compared with 92.32 ± 9.79% for free CCNU. Furthermore, in a coculture BBB model in a transwell system, coumarin-6 loaded T80-LIP displayed approximately 1.5-fold higher permeability than the uncoated formulation (Cou6@LIP) and significantly decreased glioma viability (64.37 ± 3.54%) without compromising endothelial integrity. Overall, CCNU@T80-LIP demonstrates efficient BBB translocation, pH-responsive release, and potent tumor-selective cytotoxicity, highlighting its potential as an effective nanocarrier for glioma chemotherapy.
