In vitro evaluation on novel modified chitosan for targeted antitumor drug delivery

• Published in: Carbohydrate polymers Vol. 92; no. 1; pp. 545 - 554
• Main Authors: Qu, Ding, Lin, Haijiao, Zhang, Nan, Xue, Jingwei, Zhang, Can
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 30.01.2013; Elsevier
• Subjects: adenocarcinoma; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Applied sciences; Biological and medical sciences; Breast Neoplasms - drug therapy; carbon; Cellular uptake; Chemotherapy; Chitosan; Chitosan - administration & dosage; Chitosan - analogs & derivatives; Chitosan - chemical synthesis; Chitosan - chemistry; composite polymers; drug carriers; Drug Carriers - administration & dosage; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Exact sciences and technology; Female; folic acid; Folic Acid - administration & dosage; Folic Acid - chemical synthesis; Folic Acid - chemistry; Fourier transform infrared spectroscopy; Humans; in vitro studies; MCF-7 Cells; Medical sciences; Micelles; Natural polymers; nuclear magnetic resonance spectroscopy; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymers - administration & dosage; Polymers - chemical synthesis; Polymers - chemistry; stable isotopes; Starch and polysaccharides; Tumor targeting; Cellular uptake; Chitosan; Tumor targeting; Micelles; Paclitaxel; Biological properties; Antineoplastic agent; Targeting; Cytotoxicity; Benzo[c]furan-1,3dione(1,3-dihydro); Drug carrier; Nanoencapsulation; Folic acid; Alkylation; Mechanism; Endocytosis; Micellar critical concentration; Tumor cell; Amphiphilic polymer; Control release polymer; Hydroxyalkylation; Experimental study; Chemical coupling; Chemical modification; Chitosan derivatives; Imidation; Internalization; Preparation; Oside polymer; Dialysis; Aqueous solution; Micellar solution
• ISSN: 0144-8617; 1879-1344; 1879-1344
• DOI: 10.1016/j.carbpol.2012.08.112

► Synthesis and characterization of novel amphiphilic chitosan derivates as drug delivery system. ► Introduction of phthalyl groups could lower CMC and improve solubility in aqueous and organic system. ► Drug-loaded micelles with small particle size, narrow distribution and high drug loading efficiency. ► Enhancement on cellular uptake by active tumor targeting. ► Mechanism of cellular uptake varied from different surface properties. In this study, a novel amphiphilic copolymer designed as N-octyl-N-phthalyl-3,6-O-(2-hydroxypropyl) chitosan (OPHPC) were synthesized and then conjugated with folic acid (FA-OPHPC) to produce a targeted drug carrier for tumor-specific drug delivery. OPHPC and FA-OPHPC were characterized by FT-IR, 1H NMR, 13C NMR and elemental analysis. Paclitaxel (PTX) loaded OPHPC micelles (PTX-OPHPC) with well-defined spherical shape and homogeneous distribution exhibited drug-loading rate ranging from 33.6% to 45.3% and entrapment efficiency from 50.5% to 82.8%. In the cellular uptake studies, PTX-OPHPC brought about a significantly higher amount of PTX accumulated in human breast adenocarcinoma cell line (MCF-7 cells) compared with Taxol®. Moreover, the cellular uptake of PTX in PTX loaded FA-OPHPC micelles (PTX-FA-OPHPC) was 3.2-fold improved in comparison with that of PTX-OPHPC. The results revealed that OPHPC micelle might be a promising drug carrier for promoting PTX cellular uptake and FA-OPHPC micelle could be used as a potential tumor-targeted drug vector.