Oral Delivery of Psoralidin by Mucoadhesive Surface-Modified Bilosomes Showed Boosted Apoptotic and Necrotic Effects against Breast and Lung Cancer Cells

Rana Ahmed Youness, Abdulaziz Mohsen Al-Mahallawi, Farah Haytham Mahmoud, Hind Atta, Maria Braoudaki, Sherif Ashraf Fahmy, Luminita Marin (Editor), Jianxun Ding (Editor)

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This study aims to design and optimize chitosan-coated bilosomal formulations loaded with psoralidin (Ps-CS/BLs) with improved physicochemical properties, oral bioavailability, and boosted apoptotic and necrotic effects. In this regard, uncoated bilosomes loaded with Ps (Ps/BLs) were nanoformulated using the thin-film hydration technique using different molar ratios of phosphatidylcholine (PC), cholesterol (Ch), Span 60 (S60), and sodium deoxycholate (SDC) (1:0.4:0.2:0.125, 1:0.4:0.2:0.25, and 1:0.4:0.2:0.5, respectively). The best-optimized formulation with respect to size, PDI, zeta potential, and EE% was selected and then coated with chitosan at two different concentrations (0.125 and 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. Additionally, it was demonstrated that coating Ps/BLs with chitosan has significantly increased the particle size from 123.16 ± 6.90 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 higher zeta potential (+30.78 ± 1.44 mV) as compared to Ps/BLs (−18.59 ± 2.13 mV). Furthermore, Ps-CS/BL showed 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 compared to Ps/BLs over 48 h, and both formulations were best obeying the Higuchi diffusion model. More importantly, Ps-CS/BLs displayed 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, upon evaluating the apoptotic and necrotic effects of free Ps and Ps-CS/BLs on human breast cancer cell lines (MCF-7) and human lung adenocarcinoma cell lines (A549), there was a dramatic increase in the percentages of the apoptotic and necrotic cell compared to the control and free Ps. Our findings suggest the possible oral use of Ps-CS/BLs in hampering breast and lung cancers.
Original languageEnglish
Article number1464
Pages (from-to)1-16
Number of pages16
Issue number6
Early online date15 Mar 2023
Publication statusPublished - 15 Mar 2023


  • Article
  • psoralidin
  • chitosan
  • bilosomes
  • oral delivery
  • apoptosis
  • breast cancer
  • lung cancer


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