Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery
- Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery
- 구희범; 민경현; 이상천; 박재형; Kinam Park; 정서영; 최귀원; 권익찬; 김광명
- Hydrotropic oligomer; Glycol chitosan nanoparticles; Tumor-targeting; Paclitaxel; Drug delivery; Cancer therapy
- Issue Date
- Journal of controlled release
- VOL 172, NO 3, 823-831
- 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.
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