Abstract
The systematic development of paclitaxel (PTX) and curcumin (CUR) as dual-drug-loaded lipid nanocapsules (LNCs) for treating glioblastoma (GB) is described in the current research work. As both PTX and CUR have shown substantial potential for treating various carcinomas, they were explored for treating GB. A risk-based approach to product development was used to optimize the LNC quality attributes. Using an I-optimal response surface design, the LNCs were optimized for the dual-drug-loaded LNCs. The optimized dual-drug-loaded LNCs measured 171.3 nm in diameter, polydispersity index of 0.281 with a high encapsulation efficiency (> 90%), and a drug loading capacity of 11.12%. Using the microdialysis bag method, in vitro drug release experiments demonstrated that more than 70% of the medication was released within 8 h. Furthermore, the dual drug-loaded LNCs remained stable for the period of six months. It was shown that dual drug-loaded LNCs had a greater cytotoxic effect, as seen by lower IC50 values, when tested on the C-6 glioma cell line. In vivo, the optimized LNC considerably enhanced drug absorption characteristics (C-max and AUC) over both free drugs-containing suspensions (p < 0.05). Overall, dual drug-loaded-loaded LNCs showed a synergistic cytotoxic effect and better drug release with good stability compared to those of the plain drug LNCs.
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