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Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery.
Int J Pharm. 2011 Dec 12; 421(1):160-9.IJ

Abstract

A series of novel self-assembled hyaluronic acid derivatives (HA-C(18)) grafted with hydrophobic octadecyl moiety and further dual targeting folic acid-conjugated HA-C(18) (FA-HA-C(18)) were synthesized. With the increase in the degree of substitution of octadecyl group from 12.7% to 19.3%, the critical micellar concentration of HA-C(18) copolymers decreased from 37.3 to 10.0 μg/mL. Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the HA-C(18) and FA-HA-C(18) micelles, with encapsulation efficiency as high as 97.3%. The physicochemical properties of the polymeric micelles were measured by DLS, TEM and DSC. Moreover, in vitro release behavior of PTX was investigated by dialysis bag method and PTX was released from micelles in a near zero-order sustained manner. In vitro antitumor activity tests suggested PTX-loaded HA-C(18) and FA-HA-C(18) micelles exhibited significantly higher cytotoxic activity against MCF-7 and A549 cells compared to Taxol at a lower PTX concentration. The cellular uptake experiments were conducted by quantitative assay of PTX cellular accumulation and confocal laser scanning microscopy imaging of coumarin-6 labeled HA-C(18) and FA-HA-C(18) micelles in folate receptor overexpressing MCF-7 cells. Folate and CD44 receptor competitive inhibition studies performed by fluorescence microscopy imaging suggested intracellular delivery of HA-C(18) and FA-HA-C(18) micelles were efficiently taken up via CD44 receptor-mediated endocytosis. The folate receptor-mediated endocytosis further enhanced internalized amounts of FA-HA-C(18) micelles in MCF-7 cells, as compared with HA-C(18) micelles. The internalization pathways of PTX-loaded HA-C(18) and FA-HA-C(18) micelles might include clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis. Therefore, the present study suggested that HA-C(18) and FA-HA-C(18) copolymers as biodegradable, biocompatible and cell-specific targetable nanostructure carriers, are promising nanosystems for cellular and intracellular targeting delivery of hydrophobic anticancer drugs.

Authors+Show Affiliations

Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21945183

Citation

Liu, Yanhua, et al. "Dual Targeting Folate-conjugated Hyaluronic Acid Polymeric Micelles for Paclitaxel Delivery." International Journal of Pharmaceutics, vol. 421, no. 1, 2011, pp. 160-9.
Liu Y, Sun J, Cao W, et al. Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery. Int J Pharm. 2011;421(1):160-9.
Liu, Y., Sun, J., Cao, W., Yang, J., Lian, H., Li, X., Sun, Y., Wang, Y., Wang, S., & He, Z. (2011). Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery. International Journal of Pharmaceutics, 421(1), 160-9. https://doi.org/10.1016/j.ijpharm.2011.09.006
Liu Y, et al. Dual Targeting Folate-conjugated Hyaluronic Acid Polymeric Micelles for Paclitaxel Delivery. Int J Pharm. 2011 Dec 12;421(1):160-9. PubMed PMID: 21945183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery. AU - Liu,Yanhua, AU - Sun,Jin, AU - Cao,Wen, AU - Yang,Jianhong, AU - Lian,He, AU - Li,Xin, AU - Sun,Yinghua, AU - Wang,Yongjun, AU - Wang,Siling, AU - He,Zhonggui, Y1 - 2011/09/16/ PY - 2011/07/20/received PY - 2011/09/04/revised PY - 2011/09/11/accepted PY - 2011/9/28/entrez PY - 2011/9/29/pubmed PY - 2013/1/15/medline SP - 160 EP - 9 JF - International journal of pharmaceutics JO - Int J Pharm VL - 421 IS - 1 N2 - A series of novel self-assembled hyaluronic acid derivatives (HA-C(18)) grafted with hydrophobic octadecyl moiety and further dual targeting folic acid-conjugated HA-C(18) (FA-HA-C(18)) were synthesized. With the increase in the degree of substitution of octadecyl group from 12.7% to 19.3%, the critical micellar concentration of HA-C(18) copolymers decreased from 37.3 to 10.0 μg/mL. Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the HA-C(18) and FA-HA-C(18) micelles, with encapsulation efficiency as high as 97.3%. The physicochemical properties of the polymeric micelles were measured by DLS, TEM and DSC. Moreover, in vitro release behavior of PTX was investigated by dialysis bag method and PTX was released from micelles in a near zero-order sustained manner. In vitro antitumor activity tests suggested PTX-loaded HA-C(18) and FA-HA-C(18) micelles exhibited significantly higher cytotoxic activity against MCF-7 and A549 cells compared to Taxol at a lower PTX concentration. The cellular uptake experiments were conducted by quantitative assay of PTX cellular accumulation and confocal laser scanning microscopy imaging of coumarin-6 labeled HA-C(18) and FA-HA-C(18) micelles in folate receptor overexpressing MCF-7 cells. Folate and CD44 receptor competitive inhibition studies performed by fluorescence microscopy imaging suggested intracellular delivery of HA-C(18) and FA-HA-C(18) micelles were efficiently taken up via CD44 receptor-mediated endocytosis. The folate receptor-mediated endocytosis further enhanced internalized amounts of FA-HA-C(18) micelles in MCF-7 cells, as compared with HA-C(18) micelles. The internalization pathways of PTX-loaded HA-C(18) and FA-HA-C(18) micelles might include clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis. Therefore, the present study suggested that HA-C(18) and FA-HA-C(18) copolymers as biodegradable, biocompatible and cell-specific targetable nanostructure carriers, are promising nanosystems for cellular and intracellular targeting delivery of hydrophobic anticancer drugs. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/21945183/Dual_targeting_folate_conjugated_hyaluronic_acid_polymeric_micelles_for_paclitaxel_delivery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00830-1 DB - PRIME DP - Unbound Medicine ER -