title: Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery.
abstract: In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents.
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S) and Instituto de Engenharia Biomédica (INEB), Universidade do Porto, Rua Alfredo Allen, 208, 4200-393, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Almeida
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, Avenida Trabalhador São-Carlense, São Carlos, SP, 400-13560-970, Brazil.
authors.forename: Daniella
authors.initials: D
authors.lastname: Silva
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, 4585-116, Gandra, Portugal.
authors.forename: Virginia
authors.initials: V
authors.lastname: Gonçalves
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S) and Instituto de Engenharia Biomédica (INEB), Universidade do Porto, Rua Alfredo Allen, 208, 4200-393, Porto, Portugal. bruno.sarmento@ineb.up.pt.|CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, 4585-116, Gandra, Portugal. bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D048271:Chitosan; D017239:Paclitaxel
keywords: Chitosan; Drug delivery; Micelles; Paclitaxel; Polycaprolactone