Enhanced Oral Bioavailability and Anticancer Efficacy of Fisetin by Encapsulating As Inclusion Complex with HPβCD in Polymeric Nanoparticles

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2017 Feb 4

PMID 28156161

Citations 31

Authors

Amrita Kadari

Sagarika Gudem

Hitesh Kulhari

Murali Mohan Bhandi

Roshan M Borkar

Venkata Ramana Murthy Kolapalli

Ramakrishna Sistla

Affiliations

Soon will be listed here.

Abstract

Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPβCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPβCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for in vitro anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.

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References

Kulhari H, Pooja D, Singh M, Kuncha M, Adams D, Sistla R . Bombesin-conjugated nanoparticles improve the cytotoxic efficacy of docetaxel against gastrin-releasing but androgen-independent prostate cancer. Nanomedicine (Lond). 2015; 10(18):2847-59. DOI: 10.2217/nnm.15.107. View

Kang K, Piao M, Hyun J . Fisetin induces apoptosis in human nonsmall lung cancer cells via a mitochondria-mediated pathway. In Vitro Cell Dev Biol Anim. 2014; 51(3):300-9. DOI: 10.1007/s11626-014-9830-6. View

Qiu N, Cheng X, Wang G, Wang W, Wen J, Zhang Y . Inclusion complex of barbigerone with hydroxypropyl-β-cyclodextrin: preparation and in vitro evaluation. Carbohydr Polym. 2013; 101:623-30. DOI: 10.1016/j.carbpol.2013.09.035. View

Liu M, Cao W, Sun Y, He Z . Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin. Int J Pharm. 2014; 477(1-2):159-66. DOI: 10.1016/j.ijpharm.2014.10.038. View

Tripathi R, Samadder T, Gupta S, Surolia A, Shaha C . Anticancer activity of a combination of cisplatin and fisetin in embryonal carcinoma cells and xenograft tumors. Mol Cancer Ther. 2011; 10(2):255-68. DOI: 10.1158/1535-7163.MCT-10-0606. View

Yang P, Tseng H, Peng C, Chen W, Chiu S . Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy. Int J Oncol. 2011; 40(2):469-78. DOI: 10.3892/ijo.2011.1203. View

Bhat T, Nambiar D, Pal A, Agarwal R, Singh R . Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention. Carcinogenesis. 2011; 33(2):385-93. DOI: 10.1093/carcin/bgr282. View

Gidwani B, Vyas A . Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment. Pharm Dev Technol. 2014; 21(2):161-71. DOI: 10.3109/10837450.2014.979945. View

Maurya B, Trigun S . Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats. Oxid Med Cell Longev. 2015; 2016:1972793. PMC: 4670673. DOI: 10.1155/2016/1972793. View

10.

Jeong D, Choi J, Choi Y, Jeong K, Cho E, Jung S . Complexation of fisetin with novel cyclosophoroase dimer to improve solubility and bioavailability. Carbohydr Polym. 2013; 97(1):196-202. DOI: 10.1016/j.carbpol.2013.04.066. View

11.

Joshi G, Kumar A, Sawant K . Enhanced bioavailability and intestinal uptake of Gemcitabine HCl loaded PLGA nanoparticles after oral delivery. Eur J Pharm Sci. 2014; 60:80-9. DOI: 10.1016/j.ejps.2014.04.014. View

12.

Zhao L, Feng S . Enhanced oral bioavailability of paclitaxel formulated in vitamin E-TPGS emulsified nanoparticles of biodegradable polymers: in vitro and in vivo studies. J Pharm Sci. 2010; 99(8):3552-60. DOI: 10.1002/jps.22113. View

13.

Seguin J, Brulle L, Boyer R, Lu Y, Ramos Romano M, Touil Y . Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy. Int J Pharm. 2013; 444(1-2):146-54. DOI: 10.1016/j.ijpharm.2013.01.050. View

14.

Zhang J, Jiang K, An K, Ren S, Xie X, Jin Y . Novel water-soluble fisetin/cyclodextrins inclusion complexes: Preparation, characterization, molecular docking and bioavailability. Carbohydr Res. 2015; 418:20-28. DOI: 10.1016/j.carres.2015.09.013. View

15.

Suh Y, Afaq F, Johnson J, Mukhtar H . A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. Carcinogenesis. 2008; 30(2):300-7. PMC: 2722149. DOI: 10.1093/carcin/bgn269. View

16.

Du F, Meng H, Xu K, Xu Y, Luo P, Luo Y . CPT loaded nanoparticles based on beta-cyclodextrin-grafted poly(ethylene glycol)/poly (L-glutamic acid) diblock copolymer and their inclusion complexes with CPT. Colloids Surf B Biointerfaces. 2013; 113:230-6. DOI: 10.1016/j.colsurfb.2013.09.015. View

17.

Adhami V, Syed D, Khan N, Mukhtar H . Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management. Biochem Pharmacol. 2012; 84(10):1277-81. PMC: 3813433. DOI: 10.1016/j.bcp.2012.07.012. View

18.

Noh E, Park Y, Kim J, Kim M, Kim H, Song H . Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways. Eur J Pharmacol. 2015; 764:79-86. DOI: 10.1016/j.ejphar.2015.06.038. View

19.

Madan J, Gundala S, Baruah B, Nagaraju M, Yates C, Turner T . Cyclodextrin complexes of reduced bromonoscapine in guar gum microspheres enhance colonic drug delivery. Mol Pharm. 2014; 11(12):4339-49. PMC: 4255741. DOI: 10.1021/mp500408n. View

20.

Yi C, Zhang Y, Yu Z, Xiao Y, Wang J, Qiu H . Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways. PLoS One. 2014; 9(7):e99943. PMC: 4085069. DOI: 10.1371/journal.pone.0099943. View