Abstract
Paclitaxel (Tax) is an anticancer drug with extremely low water solubility, and development of the formulation without organic solvents is highly desirable. Hydroxyapatite (HA) is a biocompatible and porous inorganic material that can be used effectively in drug delivery systems, but poor dispersibility in water limits its application. In this study, HA-decorated poly(lactide-co-glycolide) (PLG) spheres with several micrometers were prepared and characterized. PLG microspheres adsorbed Tax, independent in the HA decorating, and their water dispersibility was retained after the HA decorating. Tax-loaded HA-decorated PLG microspheres (Tax/HA/PLG) could thus be highly dispersed in water, increasing their cellular uptake. Most Tax molecules were stably adsorbed to the HA and HA-decorated PLG (HA/PLG) particles. Although the cytotoxicity of Tax-loaded HA was much lower than that of free Tax, the drug activity of Tax/HA/PLG was markedly improved. Since the morphology of microtubules was changed after the Tax/HA/PLG treatment, the HA/PLG could work as a carrier for Tax.
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References
Acharya S, Sahoo SK (2011) PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev 63:170–183. doi:10.1016/j.addr.2010.10.008
Bose S, Tarafder S (2012) Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. Acta Biomater 8:1401–1421. doi:10.1016/j.actbio.2011.11.017
Chlopek J, Morawska-Chochol A, Paluszkiewicz C, Jaworska J, Kasperczyk J, Dobrzynski P (2009) FTIR and NMR study of poly(lactide-co-glycolide) and hydroxyapatite implant degradation under in vivo conditions. Polym Degrad Stab 94:1479–1485. doi:10.1016/j.polymdegradstab.2009.05.010
Choi S, Murphy WL (2010) Sustained plasmid DNA release from dissolving mineral coatings. Acta Biomater 6:3426–3435. doi:10.1016/j.actbio.2010.03.020
Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Controll Release 161:505–522. doi:10.1016/j.jconrel.2012.01.043
Dosio F, Reddy LH, Ferrero A, Stella B, Cattel L, Couvreur P (2010) Novel nanoassemblies composed of squalenoyl-paclitaxel derivatives: synthesis, characterization, and biological evaluation. Bioconjugate Chem 21:1349–1361. doi:10.1021/bc100154g
Fonseca C, Simões S, Gaspar R (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Controll Release 83:273–286. doi:10.1016/S0168-3659(02)00212-2
Fredenberg S, Wahlgren M, Reslow M, Axelsson A (2011) The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-a review. Int J Pharm 415:34–52. doi:10.1016/j.ijpharm.2011.05.049
Ginebra MP, Canal C, Espanol M, Pastorino D, Montufar EB (2012) Calcium phosphate cements as drug delivery materials. Adv Drug Deliv Rev 64:1090–1110. doi:10.1016/j.addr.2012.01.008
Jongpaiboonkit L, Franklin-Ford T, Murphy WL (2009) Growth of hydroxyapatite coatings on biodegradable polymer microspheres. ACS Appl Mater Interfaces 1:1504–1511. doi:10.1021/am9001716
Koudelka S, Turánek J (2012) Liposomal paclitaxel formulations. J Controll Release 163:322–334. doi:10.1016/j.jconrel.2012.09.006
Lee D, Upadhye K, Kumta PN (2012) Nano-sized calcium phosphate (CaP) carriers for non-viral gene deilvery. Mater Sci Eng B 177:289–302. doi:10.1016/j.mseb.2011.11.001
Lin Y, Li Y, Ooi CP (2012) 5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy. J Mater Sci Mater Med 23:2453–2460. doi:10.1007/s10856-012-4723-2
Luo C, Wang Y, Chen Q, Han X, Liu X, Sun J, He Z (2012) Advances of paclitaxel formulations based on nanosystem delivery technology. Mini Rev Med Chem 12:434–444. doi:10.2174/138955712800493924
Lv PP, Ma YF, Yu R, Yue H, Ni DZ, Wei W, Ma GH (2012) Targeted delivery of insoluble cargo (paclitaxel) by PEGylated chitosan nanoparticles grafted with Arg-Gly-Asp (RGD). Mol Pharm 9:1736–1747. doi:10.1021/mp300051h
Nizamutdinova IT, Lee GW, Son KH, Jeon SJ, Kang SS, Kim YS, Lee JH, Seo HG, Chang KC, Kim HJ (2008) Tanshinone I effectively induces apoptosis in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells. Int J Oncol 33:485–491. doi:10.3892/ijo_00000031
Shi X, Wang Y, Ren L, Gong Y, Wang DA (2009) Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications. Pharm Res 26:422–430. doi:10.1007/s11095-008-9759-0
Singla AK, Garg A, Aggarwal D (2002) Paclitaxel and its formulations. Int J Pharm 235:179–192. doi:10.1016/S0378-5173(01)00986-3
Wang S, Wen S, Shen M, Guo R, Cao X, Wang J, Shi X (2011) Aminopropyltriethoxysilane-mediated surface functionalization of hydroxyapatite nanoparticles: synthesis, characterization, and in vitro toxicity assay. Int J Nanomedicine 6:3449–3459. doi:10.2147/IJN.S27166
Watanabe K, Nishio Y, Makiura R, Nakahira A, Kojima C (2013) Paclitaxel-loaded hydroxyapatite/collagen hybrid gels as drug delivery systems for metastatic cancer cells. Int J Pharm 446:81–86. doi:10.1016/j.ijpharm.2013.02.002
Xu Q, Czernuszka JT (2008) Controlled release of amoxicillin from hydroxyapatite-coated poly (lactic-co-glycolic acid) microspheres. J Controll Release 127:146–153. doi:10.1016/j.jconrel.2008.01.017
Zhang D, Tian A, Xue X, Wang M, Qiu B, Wu A (2012) The effect of temozolomide/poly(lactide-co-glycolide) (PLGA)/nano-hydroxyapatite microspheres on glioma U87 cells behavior. Int J Mol Sci 13:1109–1125. doi:10.3390/ijms13011109
Acknowledgments
This work was supported in part by grants from Special Coordination Funds for Promoting Science and Technology of MEXT [Improvement of Research Environment for Young Researchers (FY 2008-2012)].
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Kojima, C., Watanabe, K., Nagayasu, T. et al. Preparation of hydroxyapatite-decorated poly(lactide-co-glycolide) microspheres for paclitaxel delivery. J Nanopart Res 15, 2098 (2013). https://doi.org/10.1007/s11051-013-2098-z
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DOI: https://doi.org/10.1007/s11051-013-2098-z