Self-aggregates of 3,6-O,O'-dimyristoylchitosan derivative are effective in enhancing the solubility and intestinal permeability of camptothecin

Made available in DSpace on 2018-12-11T17:14:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fuel Cell Technologies Office Federación Española de Enfermedades Raras The aim of this work was to investigate the potential of a new 3,6-O,O’-dimyristoyl derivative amphiphilic chitosan (DMCh), in improving the solubility of camptothecin (CPT), a hydrophobic anticancer drug, and its potential oral delivery. FTIR, 1H NMR and solid-state 13C NMR spectroscopy were used to characterize DMCh and to determine its average degree of substitution (DS¯ = 6.8%). DMCh/CPT micelles size ranged from (281–357 nm), zeta potential (+32–50 mV) of encapsulation efficiency of 42–100%. The in vitro cell viability showed that DMCh/CPT micelles were able to reduce the toxicity of CPT. The in vitro permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models was increased up to ten fold when formulated into DMCh micelles, underlining the mucoadhesive properties of the nanocarrier. DMCh/CPT micelles are able to enhance CPT solubility and bioavailability while reduce its cytotoxicity, showing the great potential for intestinal delivery of hydrophobic drugs. São Carlos Institute of Chemistry University of Sao Paulo Avenida Trabalhador São-Carlense Institute for Research and Innovation in Health (i3S) and Institute of Biomedical Engineering (INEB) University of Porto, Rua Alfredo Allen, 208 Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University—UNESP, Rodovia Araraquara–Jaú, Km 1 Embrapa Instrumentação, Rua XV de Novembro 1452 IIFACTS—Institute for Research and Advanced Training in Health Sciences and Technologies, Rua Central de Gandra 1317 Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University—UNESP, Rodovia Araraquara–Jaú, Km 1