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Öğe Combination drug delivery with actively-targeted PLGA nanoparticles to overcome multidrug resistance in breast cancer(Elsevier, 2019) Tonbul, Hayrettin; Sahin, Adem; Tavukcuoglu, Ece; Esendagli, Gunes; Capan, YilmazDrug resistance is a major obstacle reducing the efficacy of cancer chemotherapy that decreases overall survival in breast cancer. P-glycoprotein (P-gp) inhibitors have potential to eliminate this problem whereas systemic usage of them such as elacridar is limited due to side effects and toxicity. This study aims to develop and evaluate paclitaxel and elacridar co-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles actively targeted to transferrin receptors to deliver anti-cancer drug and simultaneously overcome multi-drug resistance in breast cancer. In this study, PLGA nanoparticles were prepared by nanoprecipitation method and decorated with transferrin. Following characterization of the nanoparticles and drug release experiments, their efficacy was evaluated on breast cancer EMT6/AR1.0 cells which have high P-gp expression and resistance to paclitaxel. The average particle size and zeta potential of transferrin-decorated paclitaxel and elacridar co-loaded PLGA nanoparticles were 226.9 nm and - 3.9 mV, respectively. Their encapsulation efficiency was quite high (70-76%) and comparable for both paclitaxel and elacridar. Decoration with transferrin led to facilitated uptake of the nanoparticles by breast cancer cells and the combinatorial delivery of paclitaxel and elacridar through PLGA nanoparticles breached the resistance and enabled cytotoxicity. In conclusion, simultaneous and targeted delivery of nanoparticles co-loaded with P-gp inhibitors and anti-cancer drugs may be a promising approach for cancer therapy.Öğe Development and in vitro evaluation of temozolomide-loaded PLGA nanoparticles in a thermoreversible hydrogel system for local administration in glioblastoma multiforme(Elsevier, 2020) Sayiner, Ozgun; Arisoy, Sema; Comoglu, Tansel; Ozbay, Feyza Gul; Esendagli, GunesWith its ability to cross the blood-brain barrier, temozolomide (TMZ) is the first-line treatment option in glioblastoma multiforme therapy. This study aims to design TMZ-loaded PLGA nanoparticles (TMZ-PLGA-NP) in a thermoreversible hydrogel system comprising Pluronic (R) F-127. TMZ-PLGA-NP were prepared via emulsion-solvent evaporation method using dimethylformamide (DMF) as organic solvent and PVA solution as stabilizer. Experimental parameters for the formulation process and in vitro release profiles of free drug, TMZ-PLGA-NP and TMZ-PLGA-NP-loaded in hydrogel were investigated. Particle size in the range of 100-200 nm with an encapsulation efficiency of 55-70% has been obtained. In vitro studies showed that the TMZ-PLGA-NP loaded in hydrogel formulations have significantly slowed down the release process, providing controlled and sustained release. These nanoparticles were efficiently taken up by the glioblastoma cells and the TMZ released from the TMZ-PLGA-NP-loaded in hydrogel could reach to the efficiency of direct exposure to the free-drug. In conclusion, the thermoreversible hydrogel system containing TMZ-loaded PLGA nanoparticles may serve as a promising approach that could sustain long-term drug release for the treatment of residual glial tumors after surgery.Öğe Folic acid decoration of mesoporous silica nanoparticles to increase cellular uptake and cytotoxic activity of doxorubicin in human breast cancer cells(Elsevier, 2021) Tonbul, Hayrettin; Sahin, Adem; Tavukcuoglu, Ece; Ultav, Gozde; Akbas, Sedenay; Aktas, Yesim; Esendagli, GunesBreast cancer is the most frequent cancer among women and impacts over two million women each year. Although many different types of anticancer agents are available for breast cancer treatment, doxorubicin is one of the most widely used drug. However, doxorubicin related side effects such as heart failure and arrhythmia limit its usage. To overcome this limitation and improve doxorubicin effectiveness, pegylated liposomal doxorubicin formulation Doxil (R)/Caelyx (R) was developed. Although cardiotoxicity related side effects were reduced with liposomal doxorubicin formulations, a superior effect was not obtained and better approaches are still needed. In this study, it was aimed to develop a more effective doxorubicin formulation than Doxil (R) and to evaluate its anticancer activity. In order to achieve this goal, small sized mesoporous silica nanoparticles (MSNs) (similar to 50 nm) were obtained, actively targeted with folic acid conjugation and loaded with doxorubicin. The obtained nanoparticles were fully characterized, conjugation was verified, and pH dependent drug release profile was shown. The nanoparticles' anticancer activity was investigated in detail on the ZR-75-1 and T47-D breast cancer cell lines. Fluorescence microscope and flow cytometry studies revealed that the cellular uptake of doxorubicin could be enhanced with small sized MSNs. Moreover, folic acid conjugation made a tangible contribution to this effect. Additionally, similar results were also obtained in cytotoxicity studies on both cell lines. In conclusion, actively targeted small sized MSNs may be a promising approach to potentiate the anticancer effect of doxorubicin.