Development of a potential anti-cancer pulmonary nanosystem consisted of chitosan-doped LeciPlex loaded with resveratrol using a machine learning method

A novel self-assembled lecithin-based cationic nanocarrier (LeciPlex) doped with chitosan was prepared to improve Resveratrol solubility and anticancer efficacy. Using on a machine learning method based on regression analysis, LP5 (composed of lecithin, Peceol® and chitosan) was selected as the optimized one. This formula was spherical-shaped with a particle size of 59 nm, an encapsulation efficiency of 89% and a mean release time of 2.75 h together with a good mucoadhesive potential. Cascade impactor studies revealed the possible deep lung deposition of LP5 after nebulization. The safety of Resveratrol suspension and LP5 were checked on WISH cell line. Compared with Doxorubicin, both Resveratrol suspension and LP5 showed potent anticancer effects against the A549 cell line with IC50 values of 2.312, 2.200 and 1.708 μg/ml, respectively. These results indicated that the selected formula (LP5) significantly enhanced the crude drug anticancer effect by 63.2 fold and showed a higher anticancer selectivity index (>5.51). Furthermore, after 24 h, A549 up-took the LP5 more than the drug suspension by 40,000 fold. In addition, LP5 markedly induced the cellular apoptosis in A549 treated cells with a percentage of 73.1 compared to untreated cells. In conclusion, the results confirmed the enhanced lung anticancer effect, lower toxicity, and higher selectivity of the selected Resveratrol-loaded LeciPlex compared to the drug suspension. This study presents a potential nano-vesicular system for nebulization to combat lung cancer.

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Rabab Kamel, Nehal M. EL-Deeb, Haidy Abbas,
Development of a potential anti-cancer pulmonary nanosystem consisted of chitosan-doped LeciPlex loaded with resveratrol using a machine learning method, Journal of Drug Delivery Science and Technology, Volume 70, 2022, 103259, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2022.103259.