Min, Kyung Hyun Park, Kyeongsoon Kim, Yoo-Shin Bae, Sang Mun Lee, Seulki Jo, Hyung Gon Park, Rang-Woon Kim, In-San Jeong, Seo Young Kim, Kwangmeyung Kwon, Ick Chan 2024-01-20T23:30:22Z 2024-01-20T23:30:22Z 2021-08-31 2008-05-08 0168-3659 https://pubs.kist.re.kr/handle/201004/133496 To prepare a water-insoluble camptothecin (CPT) delivery carrier, hydrophobically modified glycol chitosan (HGC) nanoparticles were constructed by chemical conjugation of hydrophobic 5 beta-cholanic acid moieties to the hydrophilic glycol chitosan backbone. Insoluble anticancer drug, CPT, was easily encapsulated into HGC nanoparticles by a dialysis method and the drug loading efficiency was above 80%. CPT-encapsulated HGC (CPT-HGC) nanoparticles formed nano-sized self-aggregates in aqueous media (280-330 nm in diameter) and showed sustained release of CPT for 1 week. Also, HGC nanoparticles effectively protected the active lactone ring of CPT from the hydrolysis under physiological condition, due to the encapsulation of CPT into the hydrophobic cores in the HGC nanoparticles. The CPT-HGC nanoparticles exhibited significant antitumor effects and high tumor targeting ability towards MDA-MB231 human breast cancer xenografts subcutaneously implanted in nude mice. Tumor growth was significantly inhibited after i.v. injection of CPT-HGC nanoparticles at doses of 10 mg/kg and 30 mg/kg, compared to free CPT at dose of 30 mg/kg. The significant antitumor efficacy of CPT-HGC nanoparticles was attributed to the ability of the nanoparticles to show both prolonged blood circulation and high accumulation in tumors, as confirmed by near infrared (NIR) fluorescence imaging systems. Thus, the delivery of CPT to tumor tissues at a high concentration, with the assistance of HGC nanoparticles, exerted a potent therapeutic effect. These results reveal the promising potential of HGC nanoparticles-encapsulated CPT as a stable and effective drug delivery system in cancer therapy. (C) 2008 Elsevier B.V. All rights reserved. English ELSEVIER SELF-ASSEMBLED NANOPARTICLES MACROMOLECULAR THERAPEUTICS CARRIERS ACID MICE BIODISTRIBUTION DERIVATIVES DOXORUBICIN INHIBITION HYDROLYSIS Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy Article 10.1016/j.jconrel.2008.01.013 1 JOURNAL OF CONTROLLED RELEASE, v.127, no.3, pp.208 - 218 JOURNAL OF CONTROLLED RELEASE 127 3 208 218 scie scopus 000256271800002 2-s2.0-42049121123 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article SELF-ASSEMBLED NANOPARTICLES MACROMOLECULAR THERAPEUTICS CARRIERS ACID MICE BIODISTRIBUTION DERIVATIVES DOXORUBICIN INHIBITION HYDROLYSIS hydrophobically modified glycol chitosan nanoparticles (HGC) camptothecin (CPT) breast cancer anticancer drug delivery system cancer therapy