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    Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy
    (Elsevier Science Bv, 2011) Kilicay, Ebru; Demirbilek, Murat; Turk, Mustafa; Guven, Eylem; Hazer, Baki; Denkbas, Emir Baki
    Targeted drug delivery systems are one of the most promising alternatives for the cancer therapy. Rapid developments on nanomedicine facilitated the creation of novel nanotherapeutics by using different nanomaterials. Especially polymer based nanoparticles are convenient for this purpose. In this study; a natural polymer (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix for the production of a novel nanotherapeutic including antineoplastic agent, Etoposide and attached folic acid as a ligand on the nanoparticles. Modified solvent evaporation technique was used for the production of PHBHHX nanoparticles and the average size of the obtained PHBHHX nanoparticles were observed in the range of 180 nm and 1.5 mu m by the change in experimental conditions (i.e., homogenization rate, surfactant concentration and polymer/solvent ratio). By the increase in homogenization rate and surfactant concentration, size of the nanoparticles was decreased, while the size was increased by the increase in polymer/solvent ratio. Drug loading ratio was also found to be highly affected by polymer/drug ratio. Surface charge of the prepared nanoparticles was also investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide loaded and folic acid attached PHBHHX nanoparticles were observed as more effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX nanoparticles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated nanoparticles has the ability to selectively target to cancer cells. In addition, apoptotic/necrotic activities were evaluated for all formulations of the PHBHHX nanoparticles and parallel results with cytotoxicity tests were obtained. These studies demonstrate that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as promising for the targeted cancer therapy. (C) 2011 Elsevier B.V. All rights reserved.
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    Targeted delivery of etoposide to osteosarcoma cells using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles
    (Tubitak Scientific & Technical Research Council Turkey, 2017) Alp, Esma; Cirak, Tamer; Demirbilek, Murat; Turk, Mustafa; Guven, Eylem
    Folic acid (FA)-functionalized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles were prepared to enhance the delivery efficiency of the anticancer drug etoposide for the clinical treatment of osteosarcoma. PHBV nanoparticles were synthesized by emulsification/solvent evaporation technique and obtained in the size range of 200-250 nm and zeta potential range of -21 and -27 mV. Encapsulation efficiency and in vitro drug release were studied. The cytotoxic, apoptotic, and necrotic effects of PHBV nanoparticles were also investigated using Saos-2 osteosarcoma cells. The results obtained in this study demonstrate that etoposide-loaded and FA-functionalized PHBV nanoparticles can be successfully used for targeted treatment of osteosarcoma.