Combination and Co-delivery of Methotrexate and Curcumin: Preparation and In Vitro Cytotoxic Investigation on Glioma Cel
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ORIGINAL ARTICLE
Combination and Co-delivery of Methotrexate and Curcumin: Preparation and In Vitro Cytotoxic Investigation on Glioma Cells Basil Mujokoro 1 & Fatemeh Madani 1 & Seyedeh Sara Esnaashari 2 & Masood Khosravani 1 & Mahdi Adabi 1
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose Nanoformulations for co-delivery of multiple therapeutics and combinational therapies are expected to provide improved pharmacokinetics, reduced drug toxicities, and avert drug resistance. Methotrexate (MTX) and curcumin (CUR) were chosen as model drugs for this study primarily due to their anticancer activities in different phases of the cell cycle. Methods The nanoprecipitation technique was used to prepare CUR-, MTX-, and CUR/MTX-co-loaded poly(D,L-lactide-coglycolide) (PLGA) nanoparticles. Results Encapsulation and drug loading efficiencies were 87.9% and 8.0% for CUR-loaded PLGA nanoparticles and 81.4% and 13.5% for MTX-loaded PLGA nanoparticles, respectively. In addition, drug co-encapsulation and co-loading efficiencies were 77.2% and 6.5% for CUR and 86.1% and 15.5% for MTX, respectively. The results of cell cycle analysis indicated that CUR- and MTX-loaded PLGA nanoparticles additively complemented each other in the S and sub-G1 phases. The obtained combinational index (CI) also exhibited that CUR- and MTX-loaded PLGA nanoparticles produce additive cytotoxicity at Fa = 0.5 on U87MG glioma cells. In addition, necrosis dominates cell death in nanomediated monotherapy whereas apoptosis dominates co-delivery treatment. The highest amount of LDH released was related to co-delivery as well. Conclusion Nano-assisted combinational therapy and co-delivery can be used to obtain efficacies of drugs at lower concentrations, thus potentially increasing the therapeutic window of the drugs. Keywords Methotrexate . Curcumin . Co-delivery . PLGA . Nanoparticles . Combinational therapies
Introduction Chemotherapy is an important clinical modality in the fight against cancers. Anticancer drugs were commonly used in the treatment and management of cancers [1, 2]. Although anticancer drugs have shown appreciable clinical efficacy, there are many challenges which have resulted from chemotherapy. These challenges include insufficient efficacy to completely eradicate the disease, cancer
* Masood Khosravani [email protected] * Mahdi Adabi [email protected] 1
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
resistance, toxicity, and huge cost of drugs. One strategy which can be used to overcome most of these challenges is combinational therapy. Herein, we chose methotrexate (MTX), a folate analogue, and curcumin (CUR), a turmeric extract, for our investigations based on their combinational and co-delivery anticancer characteristics. The underlying anticancer mechani
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