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Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug.
Int J Pharm. 2010 Jul 15; 394(1-2):162-73.IJ

Abstract

A new series of amphiphilically modified chitosan molecules with long alkyl chains as hydrophobic moieties and glycol groups as hydrophilic moieties (N-octyl-O-glycol chitosan, OGC) was synthesized for use as drug carriers. The chemical structure was characterized by Fourier transform infrared, (1)H nuclear magnetic resonance, and elemental analysis. OGC could easily self-assemble to form nanomicelles in an aqueous environment and exhibited a low critical micellar concentration of 5.3-32.5mg/L. The biocompatibility and low toxicity of OGC as excipient for the dosage forms aimed at i.v. administration were confirmed by hemolysis, acute toxicity and histopathological studies. Furthermore, the possibility of solubilizing paclitaxel (PTX), a water-insoluble antitumor drug, with OGC micelles was also explored. PTX was successfully loaded into OGC micelles by using a simple dialysis process. The drug-loading capacity of OGC and stability of drug-loaded micelles were significantly affected by the degree of substitution of alkyl chains. Moreover, a series of safety studies including hemolysis, hypersensitivity, maximum tolerated dose, acute toxicity, and organ toxicity revealed that the PTX-loaded OGC micelles had advantages over the commercially available injectable preparation of PTX (Taxol((R))), in terms of low toxicity levels and increased tolerated dose. Additionally, cytotoxicity studies showed that the PTX-loaded OGC micelles were comparable to the commercial formulation, but the blank micelles were far less toxic than the Cremophor EL vehicle. These results suggest that OGC is a promising carrier for injectable PTX micelles.

Authors+Show Affiliations

Department of Pharmaceutics, China Pharmaceutical University, No. 24, Tongjiaxiang, 210009, Nanjing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20457237

Citation

Huo, Meirong, et al. "Synthesis and Characterization of Low-toxic Amphiphilic Chitosan Derivatives and Their Application as Micelle Carrier for Antitumor Drug." International Journal of Pharmaceutics, vol. 394, no. 1-2, 2010, pp. 162-73.
Huo M, Zhang Y, Zhou J, et al. Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug. Int J Pharm. 2010;394(1-2):162-73.
Huo, M., Zhang, Y., Zhou, J., Zou, A., Yu, D., Wu, Y., Li, J., & Li, H. (2010). Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug. International Journal of Pharmaceutics, 394(1-2), 162-73. https://doi.org/10.1016/j.ijpharm.2010.05.001
Huo M, et al. Synthesis and Characterization of Low-toxic Amphiphilic Chitosan Derivatives and Their Application as Micelle Carrier for Antitumor Drug. Int J Pharm. 2010 Jul 15;394(1-2):162-73. PubMed PMID: 20457237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug. AU - Huo,Meirong, AU - Zhang,Yong, AU - Zhou,Jianping, AU - Zou,Aifeng, AU - Yu,Di, AU - Wu,Yiping, AU - Li,Jing, AU - Li,Hong, Y1 - 2010/05/08/ PY - 2010/02/09/received PY - 2010/04/22/revised PY - 2010/05/04/accepted PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/9/21/medline SP - 162 EP - 73 JF - International journal of pharmaceutics JO - Int J Pharm VL - 394 IS - 1-2 N2 - A new series of amphiphilically modified chitosan molecules with long alkyl chains as hydrophobic moieties and glycol groups as hydrophilic moieties (N-octyl-O-glycol chitosan, OGC) was synthesized for use as drug carriers. The chemical structure was characterized by Fourier transform infrared, (1)H nuclear magnetic resonance, and elemental analysis. OGC could easily self-assemble to form nanomicelles in an aqueous environment and exhibited a low critical micellar concentration of 5.3-32.5mg/L. The biocompatibility and low toxicity of OGC as excipient for the dosage forms aimed at i.v. administration were confirmed by hemolysis, acute toxicity and histopathological studies. Furthermore, the possibility of solubilizing paclitaxel (PTX), a water-insoluble antitumor drug, with OGC micelles was also explored. PTX was successfully loaded into OGC micelles by using a simple dialysis process. The drug-loading capacity of OGC and stability of drug-loaded micelles were significantly affected by the degree of substitution of alkyl chains. Moreover, a series of safety studies including hemolysis, hypersensitivity, maximum tolerated dose, acute toxicity, and organ toxicity revealed that the PTX-loaded OGC micelles had advantages over the commercially available injectable preparation of PTX (Taxol((R))), in terms of low toxicity levels and increased tolerated dose. Additionally, cytotoxicity studies showed that the PTX-loaded OGC micelles were comparable to the commercial formulation, but the blank micelles were far less toxic than the Cremophor EL vehicle. These results suggest that OGC is a promising carrier for injectable PTX micelles. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/20457237/Synthesis_and_characterization_of_low_toxic_amphiphilic_chitosan_derivatives_and_their_application_as_micelle_carrier_for_antitumor_drug_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(10)00339-X DB - PRIME DP - Unbound Medicine ER -