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Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin

1
Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Korea
2
Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 46241, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2018, 10(3), 158; https://doi.org/10.3390/pharmaceutics10030158
Received: 9 August 2018 / Revised: 7 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
Co-administration of conventional and natural chemotherapeutics offers synergistic anticancer efficacy while minimizing adverse effects. In this study, an oral co-delivery system for pemetrexed (PMX) and quercetin (QCN) was designed based on water-in-oil-in-water nanoemulsion (NE), which is highly absorbable because it enhances the intestinal membrane permeability of PMX and aqueous solubility of QCN. To create this system, an ion-pairing complex of PMX with Nα-deoxycholyl-l-lysyl-methylester (DCK) was formed and further incorporated with QCN into the NE, yielding PMX/DCK-QCN-NE. The results revealed synergistic inhibitory effects on human lung carcinoma (A549) cell proliferation and migration after combined treatment with PMX/DCK and QCN. The intestinal membrane permeability and cellular uptake of PMX/DCK and QCN from the NE were significantly improved via facilitated transport of PMX by the interaction of DCK with bile acid transporters, as well as NE formulation-mediated alterations in the membrane structure and fluidity, which resulted in 4.51- and 23.9-fold greater oral bioavailability of PMX and QCN, respectively, than each free drug. Tumor growth in A549 cell-bearing mice was also maximally suppressed by 62.7% after daily oral administration of PMX/DCK-QCN-NE compared with controls. Thus, PMX/DCK-QCN-NE is a promising oral nanocarrier of PMX and QCN for synergistic anticancer efficacy and long-term chemotherapy. View Full-Text
Keywords: pemetrexed; quercetin; multiple nanoemulsion; permeability; oral bioavailability; oral anticancer therapy pemetrexed; quercetin; multiple nanoemulsion; permeability; oral bioavailability; oral anticancer therapy
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MDPI and ACS Style

Pangeni, R.; Panthi, V.K.; Yoon, I.-S.; Park, J.W. Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin. Pharmaceutics 2018, 10, 158. https://doi.org/10.3390/pharmaceutics10030158

AMA Style

Pangeni R, Panthi VK, Yoon I-S, Park JW. Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin. Pharmaceutics. 2018; 10(3):158. https://doi.org/10.3390/pharmaceutics10030158

Chicago/Turabian Style

Pangeni, Rudra, Vijay Kumar Panthi, In-Soo Yoon, and Jin Woo Park. 2018. "Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin" Pharmaceutics 10, no. 3: 158. https://doi.org/10.3390/pharmaceutics10030158

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