title: Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery.
abstract: Enhanced drug-loading and therapeutic efficacies are highly essential properties for nanoparticles as tumor-targeting drug carriers. Herein, we developed the glycol chitosan nanoparticles with hydrotropic oligomers (HO-CNPs) as a new tumor targeting drug delivery system. For enhancing drug-loading efficiency of paclitaxel in drug carriers, hydrotropic 2-(4-(vinylbenzyloxy)-N,N-diethylnicotinamide) (VBODENA-COOH) oligomers, that were used for enhancing the aqueous solubility of paclitaxel, were directly conjugated to glycol chitosan polymers. The amphiphilic conjugates readily formed nanoparticle structure (average size=302 ± 22 nm) in aqueous condition. Water-insoluble paclitaxel (PTX) was readily encapsulated into HO-CNPs with a high drug-loading amount up to 24.2 wt.% (2.4 fold higher than other polymeric nanoparticles) by a simple dialysis method. The PTX encapsulated HO-CNPs (PTX-HO-CNPs; average size=343 ± 12 nm) were very stable in aqueous media up to 50 days. Also, PTX-HO-CNPs presented rapid cellular uptake and lower cytotoxicity in cell culture system, compared to Cremophor EL/ethanol formulation of PTX. In tumor-bearing mice, the extravasation and accumulation of PTX-HO-CNPs in tumor tissue were precisely observed by intravital fluorescence imaging techniques. Furthermore, PTX-HO-CNPs showed the higher therapeutic efficacy, compared to Abraxane®, a commercialized PTX-formulation. These overall results demonstrate its potential as a new nano-sized PTX carrier for cancer treatment.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.forename: Sang Cheon
authors.initials: SC
authors.lastname: Lee
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C118638:glycol-chitosan; D048271:Chitosan; D017239:Paclitaxel
keywords: Cancer therapy; Drug delivery; Glycol chitosan nanoparticles; Hydrotropic oligomer; Paclitaxel; Tumor-targeting