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    Functionalized layer-by-layer assembled film with directional 5-fluorouracil release to target colon cancer

    Year: 2020

    Journal: Mater. Sci. Eng. C-Mater. Biol. Appl., Volume 115, OCT

    Authors: Janardhanam, Leela Sai Lokesh; Indukuri, Vikram Varma; Verma, Pratishtha; Dusane, Apurva Chandrashekhar; Venuganti, Venkata Vamsi Krishna

    Organizations: Science and Engineering Research Board, Department of Science and Technology, India [EMR/2016/005421]

    Keywords: Layer-by-layer assembled film; 5-fluorouracil; Colon cancer; Caco-2 cell spheroids; Eudragit S100 capsule

    The objective of this work was to prepare and characterize pH-sensitive capsule containing functionalized layer-by-layer (LbL) assembled polymeric film with directional drug release and evaluate its effectiveness against colon cancer. 5-Fluorouracil (5FU) loaded LbL film was prepared by sequential adsorption of chitosan and alginate polyelectrolytes. This LbL film was coated with polycaprolactone (PCL, 95% w/w) as a backing layer to restrict 5FU release on one-side. The other side constituted the folic acid conjugated chitosan layer for cancer targeting. This film was encapsulated into a gelatin capsule coated with pH-sensitive Eudragit 5100. 5FU loaded LbL film was characterized for physical and mechanical properties. Mucoadhesion studies performed using excised rabbit colon showed that chitosan-side of LbL film adhered with significantly (p < 0.05) greater strength compared with PCL-side. Non-everted rat colon-sac model and open colon membrane model studies showed greater permeation of 5FU across the colon wall when adhered to chitosan-side of LbL film compared with PCL-side of the film. Cell monolayer and 3D-spheroid model studies using Caco-2 and COLO 320DM colorectal cancer cells showed significant (p < 0.05) growth inhibition by 5FU loaded LbL film compared with free 5FU solution. In conclusion, pH-sensitive capsule containing 5FU loaded LbL film can be developed to target colorectal cancer for regional drug delivery.
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