Chitosan microparticles with modified surface chemistries as drug carriers: A study on their interactions in a simulated intestinal microenvironment.

The surface charge of drug carriers and their interactions with the biological microenvironment prevailing in the gastrointestinal tract are important parameters to be considered while designing an effective oral drug delivery system. In this work, chitosan (CS) microparticles with different surface charges were synthesized by functionalizing them with lysine (LCS) and maleic anhydride (MCS), loaded with the anti-cancer drug 5-fluorouracil (5-FU), and their properties were studied in a simulated intestinal microenvironment. The zeta potentials for CS, LCS, and MCS microparticles were + 13.3, +23.7, and - 9.54 mV, respectively. When loaded with 5-FU, the microparticles showed higher water uptake and drug release at acidic pH (CS - 96.9%, MCS - 93.4%, and LCS - 99.6%). Coating the microparticles with Eudragit®S-100 prevented drug loss in acidic conditions prevailing in the stomach and exhibited controlled release at pH 6.8 and 7.4, prevailing in the intestine. Cationic-LCS and CS microparticles exhibited better tight junction opening than anionic-MCS microparticles. The apparent permeability of 5-FU, determined across the Caco-2 cell monolayer, followed the order LCS > CS > MCS. Modified microparticles showed significantly higher mucoadhesion than CS microparticles, which is desirable for better retention (p-value ≤0.01). Lower mucin interaction exhibited by microparticles facilitates mucopenetration. The calculated IC50 values of 5-FU-loaded in LCS microparticles on Caco-2 cells were 1065 μM after 24 h, 452 μM after 48 h, and 177 μM after 72 h. Among the CS systems, LCS exhibited improved paracellular permeability of 5-FU and mucoadhesion and was better suited as an oral drug delivery vehicle.