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Arjun Patra,1,2,* Swaha Satpathy,1,2,* Anitha K Shenoy,1 Jason A Bush,3 Mohsin Kazi,4 Muhammad Delwar Hussain1,* 1College of Pharmacy, Department of Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, CA, USA; 2Institute of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur (C.G.), India; 3Department of Biology, California State University, Fresno, CA, USA; 4Kayyali Chair for Pharmaceutical Industries, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia *These authors contributed equally to this work Background: Quercetin (QCT), a naturally occurring flavonoid has a wide array of pharmacological properties such as anticancer, antioxidant and anti-inflammatory activities. QCT has low solubility in water and poor bioavailability, which limited its use as a therapeutic molecule. Polymeric micelles (PMs) is a novel drug delivery system having characteristics like smaller particle size, higher drug loading, sustained drug release, high stability, increased cellular uptake and improved therapeutic potential. In the present study, we have formulated and characterized mixed PMs (MPMs) containing QCT for increasing its anticancer potential. Methods: The MPMs were prepared by thin film hydration method, and their physicochemical properties were characterized. The in vitro anticancer activity of the MPMs were tested in breast (MCF-7 and MDA-MB-231, epithelial and metastatic cancer cell lines, respectively), and ovarian (SKOV-3 and NCI/ADR, epithelial and multi-drug resistant cell lines, respectively) cancer. Results: The optimal MPM formulations were obtained from Pluronic polymers, P123 and P407 with molar ratio of 7:3 (A16); and P123, P407 and TPGS in the molar ratio of 7:2:1 (A22). The size of the particles before lyophilization (24.83±0.44 nm) and after lyophilization (37.10±4.23 nm), drug loading (8.75±0.41%), and encapsulation efficiency (87.48±4.15%) for formulation A16 were determined. For formulation A22, the particle size before lyophilization, after lyophilization, drug loading and encapsulation efficiency were 26.37±2.19 nm, 45.88±13.80 nm, 9.01±0.11% and 90.07±1.09%, respectively. The MPMs exhibited sustained release of QCT compared to free QCT as demonstrated from in vitro release experiments. The solubility of QCT was markedly improved compared to pure QCT. The MPMs were highly stable in aqueous media as demonstrated by their low critical micelle concentration. The concentration which inhibited 50% growth (IC50) values of both micellar preparations in all the cancer cell lines were significantly less compared to free QCT. Conclusion: Both the MPMs containing QCT could be used for effective delivery to different type of cancer and may be considered for further development. Keywords: quercetin, mixed polymeric micelle, Pluronics, TPGS, breast cancer, ovarian cancer, multidrug resistant cancer |
