Polymeric nanoparticles of cholesterol-modified glycol chitosan for doxorubicin delivery: preparation and in-vitro and in-vivo characterization.
OBJECTIVE
Polymeric nanoparticles have been extensively studied as drug carriers. Chitosan and its derivatives have attracted significant attention in this regard but have limited application because of insolubility in biological solution. In this work, we attempted to utilize cholesterol-modified glycol chitosan (CHGC) self-aggregated nanoparticles to increase aqueous solubility, and to reduce side effects and enhance the antitumour efficacy of the anticancer drug doxorubicin. Methods CHGC nanoparticles were loaded with doxorubicin by a dialysis method, and their characteristics were determined by transmission electron microscopy examination, light-scattering study, in-vitro drug-release study, pharmacokinetic study in rats and in-vivo antitumour activity in mice.


RESULTS
The resulting doxorubicin-loaded CHGC nanoparticles (DCNs) formed self-assembled aggregates in aqueous medium. From the observation by transmission electron microscopy, DCNs were almost spherical in shape. The mean diameters of these nanoparticles determined by dynamic light scattering were in the range of 237-336 nm as the doxorubicin-loading content increased from 1.73% to 9.36%. In-vitro data indicated that doxorubicin release from DCNs was much faster in phosphate-buffered saline at pH 5.5 than at pH 6.5 and 7.4, and the release rate was dependent on the loading content of doxorubicin in these nanoparticles. It was observed that DCN-16 (drug loaded content: 9.36%) exhibited prolonged circulation time in rat plasma and showed higher antitumour efficacy against S180-bearing mice than free doxorubicin.


CONCLUSIONS
These results indicated that CHGC nanoparticles had potential as a carrier for insoluble anticancer drugs in cancer therapy.
Yu
Jing-Mou
JM
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Li
Yong-Jie
YJ
Qiu
Li-Yan
LY
Jin
Yi
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002784:Cholesterol / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D004339:Drug Compounding; D008027:Light; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D012995:Solubility; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011108:Polymers; C118638:glycol-chitosan; D004317:Doxorubicin; D048271:Chitosan; D002784:Cholesterol