Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers
- Patra A. [2] ,
- Satpathy S. [2] ,
- Shenoy A.K. [1] ,
- Bush J.A. [3] ,
- Kazi M. [4] ,
- Hussain M.D. [1] ,
- Shenoy A. and
- Bush J.
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Description
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 lyophilisation (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.
Subjects
Affiliations
- College of Pharmacy, Department of Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, CA, USA.
- College of Pharmacy, Department of Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, CA, USA. Institute of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur (C.G.), India.
- Department of Biology, California State University, Fresno, CA, USA.
- Kayyali Chair for Pharmaceutical Industries, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.