Folate-decorated poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting delivery: optimization and in vivo antitumor activity |
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Authors: | Chan Zhang Zhuo Zhang Liangqi Zhao |
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Institution: | 1. School of Environment and Safety, Taiyuan University of Science and Technology, Taiyuan, P.R. China, zhang_chan@yahoo.com;3. College of Urban and Environmental Science, Liaoning Normal University, Dalian, P.R. China, and;4. Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, P.R. China |
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Abstract: | AbstractContext: Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) P(HB-HO)] nanoparticles DOX/FA-PEG-P(HB-HO) NPs] have potential application in clinical treatments for cervical cancer due to specific affinity of folate and folate receptor in HeLa cells.Objective: The aim of this study was to develop an optimized formulation for DOX/FA-PEG-P(HB-HO) NPs, and investigate the targeting and efficacies of the nanoparticles.Materials and methods: DOX/FA-PEG-P(HB-HO) NPs were prepared by W1/O/W2 solvent extraction/evaporation method, and an orthogonal experimental design L9 (34)] was applied to establish the optimum conditions. The physico–chemical characteristics, microscopic observation and in vivo antitumor study of the nanoparticles were evaluated.Results: The optimum formulation was obtained with DOX 10% (w/v), FA-PEG-P(HB-HO) 6.5% (w/v), PVA 3%(w/v) and oil phase/internal water phase volume ratio of 3/1. The size distribution, drug loading and encapsulation efficiency of the optimized nanoparticles were 150–350?nm, 29.6?±?2.9% and 83.5?±?5.7%, respectively. In vitro release study demonstrated that 80% of the drug could release from the nanoparticles within 11 days. Furthermore, in vitro microscopic observation and in vivo antitumor study showed that DOX/FA-PEG-P(HB-HO) NPs could inhibit HeLa cells effectively, and the tumor inhibition rate (TIR) in vivo was 76.91%.Discussion and conclusions: DOX/FA-PEG-P(HB-HO) NPs have been successfully developed and optimized. In vitro drug release study suggested a sustained release profile. Moreover, DOX/FA-PEG-P(HB-HO) NPs could effectively inhibit HeLa cells with satisfying targeting, and reduce side effects and toxicity to normal tissues. DOX/FA-PEG-P(HB-HO) NPs were superior in terms of inhibiting HeLa tumor over non-targeted formulations therapy. |
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Keywords: | Doxorubicin folate-targeted nanoparticles in vivo antitumor activity orthogonal design poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) |
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