Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting

The Cur-FPPs’ preparing flow chart and cellular uptake on MCF-7 and HepG2 cells in vitro. •The folate-modified Curcumin loaded micelles (Cur-FPPs) were prepared by thin-film hydration method.•The Cur-FPPs increased the cytotoxicity and cellular uptake of Cur on MCF-7 and HepG2 cells in vitro.•The Cu...

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Veröffentlicht in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2014-09, Vol.121, p.206-213
Hauptverfasser: Yang, Chunfen, Chen, Hao, Zhao, Jie, Pang, Xin, Xi, Yanwei, Zhai, Guangxi
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container_start_page 206
container_title Colloids and surfaces, B, Biointerfaces
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creator Yang, Chunfen
Chen, Hao
Zhao, Jie
Pang, Xin
Xi, Yanwei
Zhai, Guangxi
description The Cur-FPPs’ preparing flow chart and cellular uptake on MCF-7 and HepG2 cells in vitro. •The folate-modified Curcumin loaded micelles (Cur-FPPs) were prepared by thin-film hydration method.•The Cur-FPPs increased the cytotoxicity and cellular uptake of Cur on MCF-7 and HepG2 cells in vitro.•The Cur-FPPs prolonged the half-life of Cur in rats. Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.
doi_str_mv 10.1016/j.colsurfb.2014.05.005
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Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.</description><identifier>ISSN: 0927-7765</identifier><identifier>EISSN: 1873-4367</identifier><identifier>DOI: 10.1016/j.colsurfb.2014.05.005</identifier><identifier>PMID: 24984268</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Cancer ; Cell Death - drug effects ; Cell Survival - drug effects ; Cellular ; Charge coupled devices ; Curcumin ; Curcumin - administration &amp; dosage ; Curcumin - pharmacokinetics ; Curcumin - pharmacology ; Curcumin - therapeutic use ; Delivery systems ; Drug Delivery Systems ; Endocytosis - drug effects ; Folate ; Folic Acid - chemistry ; Formulations ; Hemolysis - drug effects ; Hep G2 Cells ; Humans ; In vitro testing ; Irritants - pharmacology ; Lactic Acid - chemical synthesis ; Lactic Acid - chemistry ; Male ; MCF-7 Cells ; Micelles ; Microscopy, Fluorescence ; mPEG-PLA ; Nanostructure ; Neoplasms - drug therapy ; Particle Size ; Polyesters ; Polyethylene Glycols - chemical synthesis ; Polyethylene Glycols - chemistry ; Polymers - chemical synthesis ; Polymers - chemistry ; Rabbits ; Rats ; Static Electricity ; Surface-Active Agents - chemical synthesis ; Surface-Active Agents - chemistry</subject><ispartof>Colloids and surfaces, B, Biointerfaces, 2014-09, Vol.121, p.206-213</ispartof><rights>2014</rights><rights>Crown Copyright © 2014. Published by Elsevier B.V. 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Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.</description><subject>Animals</subject><subject>Cancer</subject><subject>Cell Death - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cellular</subject><subject>Charge coupled devices</subject><subject>Curcumin</subject><subject>Curcumin - administration &amp; dosage</subject><subject>Curcumin - pharmacokinetics</subject><subject>Curcumin - pharmacology</subject><subject>Curcumin - therapeutic use</subject><subject>Delivery systems</subject><subject>Drug Delivery Systems</subject><subject>Endocytosis - drug effects</subject><subject>Folate</subject><subject>Folic Acid - chemistry</subject><subject>Formulations</subject><subject>Hemolysis - drug effects</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>In vitro testing</subject><subject>Irritants - pharmacology</subject><subject>Lactic Acid - chemical synthesis</subject><subject>Lactic Acid - chemistry</subject><subject>Male</subject><subject>MCF-7 Cells</subject><subject>Micelles</subject><subject>Microscopy, Fluorescence</subject><subject>mPEG-PLA</subject><subject>Nanostructure</subject><subject>Neoplasms - drug therapy</subject><subject>Particle Size</subject><subject>Polyesters</subject><subject>Polyethylene Glycols - chemical synthesis</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Polymers - chemical synthesis</subject><subject>Polymers - chemistry</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Static Electricity</subject><subject>Surface-Active Agents - chemical synthesis</subject><subject>Surface-Active Agents - chemistry</subject><issn>0927-7765</issn><issn>1873-4367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhL1Q-ckkYO_7KDVTKh1SJCxyR5djjyqskXuxkpf33ZLUt13IajfS8M6N5CLlh0DJg6sO-9Xmsa4lDy4GJFmQLIF-QHTO6a0Sn9Euyg57rRmslr8ibWvcAwAXTr8kVF70RXJkd-f0Zjzjmw4TzQnOkjsY8ugWbKYcUEwbq1-LXKc10zC5s_ZQ8jiPSgGM6YjnReqoLTluuUO9mj4UurjzgkuaHt-RVdGPFd4_1mvz6cvfz9ltz_-Pr99tP940XnVga4bkzEjslYq97HdjgjOo9INMdQB_7YAbplI8GvA8Q-CBFjOgddizqgXfX5P1l7qHkPyvWxU6pns90M-a1WqYE7zjrFPwHynUvTM_F86iUzDCjgG2ouqC-5FoLRnsoaXLlZBnYszC7t0_C7FmYBWk3YVvw5nHHOkwY_sWeDG3AxwuA2_-OCYutPuH25pAK-sWGnJ7b8Rewm6tq</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Yang, Chunfen</creator><creator>Chen, Hao</creator><creator>Zhao, Jie</creator><creator>Pang, Xin</creator><creator>Xi, Yanwei</creator><creator>Zhai, Guangxi</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20140901</creationdate><title>Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting</title><author>Yang, Chunfen ; 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Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24984268</pmid><doi>10.1016/j.colsurfb.2014.05.005</doi><tpages>8</tpages></addata></record>
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subjects Animals
Cancer
Cell Death - drug effects
Cell Survival - drug effects
Cellular
Charge coupled devices
Curcumin
Curcumin - administration & dosage
Curcumin - pharmacokinetics
Curcumin - pharmacology
Curcumin - therapeutic use
Delivery systems
Drug Delivery Systems
Endocytosis - drug effects
Folate
Folic Acid - chemistry
Formulations
Hemolysis - drug effects
Hep G2 Cells
Humans
In vitro testing
Irritants - pharmacology
Lactic Acid - chemical synthesis
Lactic Acid - chemistry
Male
MCF-7 Cells
Micelles
Microscopy, Fluorescence
mPEG-PLA
Nanostructure
Neoplasms - drug therapy
Particle Size
Polyesters
Polyethylene Glycols - chemical synthesis
Polyethylene Glycols - chemistry
Polymers - chemical synthesis
Polymers - chemistry
Rabbits
Rats
Static Electricity
Surface-Active Agents - chemical synthesis
Surface-Active Agents - chemistry
title Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting
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