Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: synthesis, characterization, and in vivo biodistribution.
Development of successful formulations for poorly water-soluble drugs remains a longstanding critical and challenging issue in cancer therapy. As a potential drug carrier of paclitaxel, hydrotropic oligomer-glycol chitosan (HO-GC) was synthesized by chemical conjugation of the N,N-diethylnicotinamide-based oligomer, uniquely designed for enhancing the aqueous solubility of paclitaxel, to the backbone of glycol chitosan. Owing to its amphiphilicity, the conjugate formed self-assembled nanoparticles with a mean diameter of 313+/-13nm in a phosphate-buffered saline (PBS, pH 7.4 at 37 degrees C). HO-GC nanoparticles maintained their structure for up to 50days in PBS. They could encapsulate a high quantity (20wt.%) of paclitaxel (PTX) with a maximum drug-loading efficiency of 97%, due to the presence of hydrotropic inner cores. When HO-GC-PTX particles were exposed to the 0.1M sodium salicylate solution in PBS (pH 7.4), PTX was released from nanoparticles in a sustained manner. From the cytotoxicity test, it was confirmed that HO-GC-PTX nanoparticles showed lower cytotoxicity than free PTX formulation in 50%/50% Cremophor EL/ethanol mixture. The optical imaging results indicated that near-infrared fluorescence dye (Cy5.5)-labeled HO-GC-PTX showed an excellent tumor specificity in SCC7 tumor-bearing mice, due to the enhanced permeation and retention effect. Overall, HO-GC-PTX nanoparticles might be a promising carrier for PTX delivery in cancer therapy.
Saravanakumar
G
G
Department of Advanced Polymer and Fiber Materials, Kyung Hee University, Gyeonggi-do 446-701, Republic of Korea.
Min
Kyung Hyun
KH
Min
Dong Sik
DS
Kim
Ah Young
AY
Lee
Chang-Moon
CM
Cho
Yong Woo
YW
Lee
Sang Cheon
SC
Kim
Kwangmeyung
K
Jeong
Seo Young
SY
Park
Kinam
K
Park
Jae Hyung
JH
Kwon
Ick Chan
IC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006018:Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013816:Thermodynamics; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006018:Glycols; D048271:Chitosan; D017239:Paclitaxel