Chitosomes Loaded Psoralidin: A Magic Bullet for the Oral Treatment of Lung Cancer

R.A. Youness , A.M. Al-Mahallawi, F.H. Mahmoud, H. Atta, M. Braoudaki, S.A. Fahmy
University of Hertfordshire-Egypt Campus,
Egypt

Keywords: natural compounds, psoralidin, chitosan, bilosomes, oral delivery, apoptosis, lung cancer

Summary:

This study aims to design and optimize chitosan-coated bilosomal formulations (BLs) loaded with the natural compound, psoralidin (Ps), forming Ps-CS/BLs to improve its physicochemical properties, oral bioavailability, and anticancer effects through boosting apoptotic and necrotic effects. In this regard, uncoated bilosomes loaded with Ps (Ps/BLs) were developed using the thin-film hydration method using different molar ratios of phosphatidylcholine (PC), cholesterol (Ch), Span 60 (S60), and sodium deoxycholate (SDC), as presented in Scheme 1. The best-optimized formulation with respect to size, PDI, zeta potential, and EE% was selected and then coated with chitosan at a concentration of 0.25 w/v%), forming Ps-CS/BLs. The optimized Ps/BLs and Ps-CS/BLs showed a spherical shape and relatively homogenous size with negligible apparent agglomerations. Also, It was demonstrated that coating Ps/BLs with chitosan has significantly increased the particle size from 123.16 ± 6.90 nm, in the case of Ps/BLs to 183.90 ± 15.93 nm, in the case of Ps-CS/BLs. In addition, Ps-CS/BLs exhibited a higher zeta potential (+30.78 ± 1.44 mV ) as compared to Ps/BLs (-18.59 ± 2.13 mV) and enhanced entrapment efficiency (EE%) of 92.15 ± 7.20% as compared to Ps/BLs (68.90 ± 5.95 %). Moreover, Ps-CS/BLs exhibited a more sustained release behavior of Ps than Ps/BLs over 48 h and both formulations were best obeying the Higuchi diffusion model. More importantly, Ps-CS/BLs exhibited the highest mucoadhesive efficiency% (74.89 ± 3.5%) as compared to Ps/BLs (26.78 ± 2.9%), indicating the ability of the designed nanoformulation to improve oral bioavailability and extend the residence time inside the gastrointestinal tract, upon oral administration. Moreover and upon evaluating the apoptotic and necrotic effects of free Ps and Ps-CS/BLs human lung adenocarcinoma cell line (A549), there was a dramatic increase in the percentages of the apoptotic and necrotic cells compared to the control and free Ps. Our findings suggest the possible oral use of Ps-CS/BLs as a magic bullet in conquering lung cancers.