Paclitaxel-Loaded N-Octyl-O-sulfate Chitosan Micelles for Superior Cancer Therapeutic Efficacy and Overcoming Drug Resistance

Abstract

Copyright: Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Macromolecular drug carriers have attracted much attention taking advantage of passive tumor targeting property and excellent biocompatibility. For many biomedical applications, however, the effectiveness of the carriers is insufficient, which complicate further development into clinical use. Here, we systematically investigated the effects of molecular weight (from 1KDa to 300KDa) of macromolecular drug carrier, octyl chitosan, on tumor accumulation and penetration, as well as drug loading and releasing profiles. It was found that the molecular weight of chitosan influenced the cellular uptake and pharmacokinetic behavior of the nanocarriers, which ultimately determined their drug delivery efficiency. Interestingly, increased molecular weight of chitosan decreased its cellular uptake but increased its resident time in blood, which provided ample time for tumor accumulation. Moreover, the molecular weight altered the drug loading capability and release profile. Our results demonstrated that 10KDa octyl chitosan was an ideal candidate for anticancer drug delivery, which could deliver anticancer agent to tumor tissues and release drugs in tumor cells more effectively than those of other molecular weights, and finally result in better therapeutic effect.

Applications of Nanoparticles for Anticancer Drug Delivery: A Review

“…329 In a nude mice xenograft model, doxorubicin-loaded PLGA-PEG polymeric micelle formulation was shown to increase tumor uptake and significant tumor regression. 330 These studies suggest the feasibility and utility of polymeric micelles in drug delivery for future targeted therapy applications. Jin et al used N-octyl-O-sulfate chitosan to form paclitaxel-encapsulated micelles and showed the micelles could inhibit P-gp-mediated paclitaxel efflux and increase cellular uptake.…”

Polymeric nanoparticles for targeted treatment in oncology: current insights

“…Jin et al explored the utility of PTX-loaded N-octyl-O-sulfate chitosan micelles for treating multidrug-resistant (MDR) cancer. 87 These micelles exhibited high cellular uptake about twofold more than Taxol, and the low efflux of PTX resulted in the optimal cytotoxicity in both human hepatocellular liver carcinoma (HepG2) cells and the MDR HepG2 (HepG2-P) cells. Intravenous injection of PTX-loaded micelles into the tumor-bearing mice demonstrated high tumor inhibition rate of 75.5% than that of Taxol (45.3%).…”

Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy

“…In vitro cytotoxicity demonstrated IC 50 Jin et al synthesized amphiphilic graft copolymer, N-octyl-O-sulfate chitosan (NOSC), and its PTX-encapsulated micelles (PTX-M) in order to overcome multidrug resistance [103]. In vitro cytotoxicity on both the human hepatocellular liver carcinoma (HepG2) cells and the multidrug resistance HepG2 (HepG2-P) cells demonstrated PTX-M presented the highest cellular uptake and the lowest efflux rate of PTX, which was due to a combination of the inhibiting P-gp effect of NOSC and the bypassing P-gp action of the intact PTX-M.…”