Optimizing molecular weight of octyl chitosan as drug carrier for improving tumor therapeutic efficacy
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Min Zhang1,*, Yi Ma1,*, Zhaohui Wang1, Zhihao Han1, Weidong Gao1 and Yueqing Gu1
1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
*These authors have contributed equally to this work
Yueqing Gu, email: [email protected]
Keywords: molecular weight, octyl chitosan, drug delivery, therapeutic efficacy improvement, reduced side effect
Received: March 07, 2017 Accepted: April 26, 2017 Published: July 22, 2017
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.
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