EVALUATION OF GENISTEIN-LOADED MICROEMULSION FORMULATION FOR ORAL DRUG DELIVERY SYSTEM: IN VITRO DRUG RELEASE AND IN VIVO PHARMACOKINETICS
Từ khóa
Tóm tắt
Background: Genistein, a bioactive soy isoflavone with anticancer and antioxidant properties, has poor solubility and low oral bioavailability, limiting its therapeutic potential. Method: An oil-in-water microemulsion (ME) system was developed to enhance genistein delivery. In vitro dissolution studies were conducted at pH 1.2 and 7.4, and pharmacokinetic studies in rats were performed to assess drug absorption. Stability was evaluated over 3 months. Result: ME formulations (ME01 - ME05) exhibited significantly higher drug release than suspension. ME05 achieved a markedly improved Cmax (78.41 ± 4.70 μg/ mL) and AUC0→∞ (623.56 ± 46.72 μg·h/mL) compared to suspension (3.57 ± 0.22 μg/mL and 37.70 ± 0.65 μg·h/mL, respectively). The ME system maintained stability over 3 months. Conclusion: Microemulsions significantly enhance genistein’s solubility, dissolution rate, and oral bioavailability, making them a promising approach for improving the therapeutic effectiveness of poorly water-soluble drugs.
Lượt tải
Tài liệu tham khảo
1. Panche, A. N., Diwan, A. D. & Chandra, S. R. Flavonoids: an overview. J. Nutr. Sci. 5, 47-62 (2016).
2. Heim, K. E., Tagliaferro, A. R. & Bobilya, D. J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem. 13(10), 572-584 (2002).
3. Thangavel, P. et al. Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases. Molecules 24, 3892 (2009).
4. Yang, Z. et al. Bioavailability and pharmacokinetics of Genistein: Mechanistic studies on its ADME. Anticancer Agents Med. Chem. 12(12), 1264- 1280 (2012).
5. Morabito, N. et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: A randomized double-blind placebo-controlled study. J. Bone Miner. Res. 17, 1904-1912 (2002).
6. Ghosh, P. & Murthy, R. Microemulsions: A Potential Drug Delivery System. Current Drug Delivery 3(2), 167-180 (2006).
7. Gibaud, S. & Attivi, D. Microemulsions for oral administration and their therapeutic applications. Expert Opin. Drug Deliv. 9(8), 937-951 (2012).
8. Kwon, S. H. et al. Comparison of oral bioavailability of genistein and genistin in rats. Int. J. Pharm. 337(1-2), 148-154 (2007).
9. Coldham, N.G. et al. Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity. Eur. J. Drug Metab. and Pharmacokinet. 27(4), 249-258 (2002).
10. Zhou, S. et al. Dose-dependent absorption, metabolism, and excretion of genistein in rats. J. Agric. Food Chem. 56(18), 8354-8359 (2008).
11. Soucy, N.V. et al. Kinetics of genistein and its conjugated metabolites in pregnant Sprague- Dawley rats following single and repeated genistein administration. Toxicol. Sci. 90(1), 230- 240 (2006).
12. Andrade, J.E. et al. Absolute bioavailability of isoflavones from soy protein isolate-containing food in female BALB/c mice. J. Agric. Food Chem. 58(7), 4529-4536 (2010).
13. Yang, Z. et al. Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC-MS/MS method: Application to an oral bioavailability study of genistein in mice. J. Pharm. Biomed. Anal. 53(1), 81–89 (2010).
14. Kim, J.T. et al. Absorption study of genistein using solid lipid microparticles and nanoparticles: control of oral bioavailability by particle sizes. Biomol. Ther. (Seoul) 25(4), 452–459 (2017).
15. Vu, Q.L. et al. Enhancement of the Topical Bioavailability and Skin Whitening Effect of Genistein by Using Microemulsions as Drug Delivery Carriers. Pharmaceuticals 14, 1233 (2021).
16. Ding, P. et al. Solutol®HS15 + pluronicF127 and Solutol®HS15+pluronicL61 mixed micelle systems for oral delivery of genistein. Drug Des. Devel. Ther. 13, 1947-1956 (2019).
17. Azeem, A., Ahmad, F.J. & Khar, R.K. Talegaonkar, S. Nanocarrier for the transdermal delivery of an antiparkinsonian drug. AAPS PharmSciTech 10, 1093-1103 (2009).
18. Tsai, M.J. et al. Nanocarriers enhance the transdermal bioavailability of resveratrol: In-vitro and in-vivo study. Colloids Surf. B Biointerfaces 148, 650-665 (2016).
