Andreia Almeida 1, Marco Araújo 2, Ramon Novoa-Carballal 3, Fernanda Andrade 4, Hugo Gonçalves 5, Rui L Reis 3, Marlene Lúcio 6, Simó Schwartz Jr 7, Bruno Sarmento 8


Chitosan was grafted with O-methyl-O’-succinylpolyethylene glycol and oleic acid after a two-step carbodiimide coupling. The structural and physicochemical characterization of the compounds confirmed the successful conjugation of the hydrophilic and hydrophobic moieties to the chitosan backbone. The amphiphilic chitosan derivative obtained allowed the formation of polymeric micelles with an average size of 140 nm, a polydispersity index <0.234, and a positive superficial charge. Camptothecin, used as a model hydrophobic drug, was successfully carried into the polymeric micelles with an encapsulation efficiency of 78%. The in vitro drug release was evaluated in simulated gastrointestinal fluids, exhibiting a low release of camptothecin in gastric media and a controlled release in intestinal fluids. Furthermore, it was demonstrated that chitosan micelles were able to stabilize camptothecin, protecting up to 75% of the drug from hydrolysis, preserving its active lactone form. This new chitosan amphiphilic system exhibits great potential to load hydrophobic drugs, acting as a promising delivery system. Keywords: Acylated chitosan; Amphiphilic chitosan derivatives; Camptothecin; Pegylated chitosan; Self-assembly.

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