Rabab Kamel

Egypt

A machine learning approach to design a chitosan-doped LeciPlex nanosystem loaded with Resveratrol for nebulization in cancer therapy

Rabab Kamel a,*
Nehal M. EL-Deeb b
Haidy Abbas c
a Pharmaceutical Technology Department, National Research Centre, Cairo, 12622, Egypt

b Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, The City of Scientific Research and Technological
Applications, New Borg El-Arab City, 21934, Alexandria, Egypt

c Pharmaceutics Department, Faculty of Pharmacy, Damanhour University, Egypt

Abstract

Background

Lung cancer remains a leading cause of cancer-related deaths, with non-small-cell lung cancer (NSCLC) being particularly lethal. Despite advancements in treatment options, prognosis for many patients remains unsatisfactory. The employment of a novel nanoformulation for non-toxic active agents can be a solution.

Methods

A novel, chitosan-doped lecithin-based nanocarrier (LeciPlex) was developed to enhance the solubility and anticancer efficacy of Resveratrol.

Results

Using a machine learning regression model, LP5 (composed of lecithin, Peceol®, and chitosan) was identified as the optimal formulation. LP5 exhibited spherical particles of 59 nm, an encapsulation efficiency of 89%, a mean release time of 2.75 hours, and strong mucoadhesion. Cascade impactor studies demonstrated its potential for deep lung deposition after nebulization. Safety assessments on WISH cells confirmed the non-toxicity of both Resveratrol suspension and LP5. In vitro studies against the A549 cell line revealed that LP5 significantly enhanced the anticancer activity of Resveratrol compared to the drug suspension, with an IC50 value of 1.708 ?g/ml. This represented a 63.2-fold increase in efficacy and a higher selectivity index (>5.51). Cellular uptake studies showed that A549 cells took up LP5 40,000 times more efficiently than the drug suspension. Moreover, LP5 markedly induced apoptosis in A549 cells reaching 73.1%.

Conclusions

These findings highlight the improved lung anticancer efficacy, reduced toxicity, and increased selectivity of Resveratrol-loaded LeciPlex compared to the drug suspension. This study presents a promising nanocarrier system for the nebulization of Resveratrol in the treatment of lung cancer.

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