Novel Self-nanomicellizing Solid Dispersion Based on Rebaudioside A: a Potential Nanoplatform for Oral Delivery of Curcumin

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2019 Jan 23

PMID 30666114

Citations 13

Authors

Yuzhen Hou

Hui Wang

Fan Zhang

Fengyuan Sun

Meng Xin

Mengshuang Li

Jun Li

Xianggen Wu

Affiliations

Soon will be listed here.

Abstract

Purpose: Rebaudioside A (RA) has nanocarrier characteristics that allow it to self-assemble into micelles in aqueous solutions. The purpose of this study was to determine if a self-nanomicellizing solid dispersion based on RA could be utilized as an oral nano-drug delivery system.

Materials And Methods: Curcumin (Cur) served as a model hydrophobic drug, and a Cur-loaded self-nanomicellizing solid dispersion based on RA (RA-Cur) was formulated. The properties of RA-Cur in the solid state and in aqueous solution were characterized. The antioxidant activity and mechanism of RA-Cur endocytosis were also investigated. The pharmacokinetics, biodistribution in the intestinal tract, and anti-inflammation properties were also evaluated in vivo.

Results: RA-Cur could be easily fabricated, and it self-assembled into ultrasmall micelles (particle size ~4 nm) in a homogeneous distribution state (polydispersity index <0.2) when dissolved in water. Cur was readily encapsulated into RA micelles and this improved its water solubility (to 14.34±1.66 mg/mL), as well as its in vitro release and membrane permeability. The antioxidant activities of Cur in RA-Cur were also significantly improved. Biodistribution in the intestinal tract confirmed a significant enhancement of Cur absorption in the duodenum, jejunum, and ileum by encapsulation in RA-Cur, and the absorption of RA-Cur was governed by mixed transcytosis mechanisms. Pharmacokinetic tests of RA-Cur in rats revealed a dramatic 19.06-fold enhancement of oral bioavailability when compared to free Cur. More importantly, oral administration of RA-Cur could efficiently ameliorate ulcerative colitis in a mouse model induced by dextran sodium sulfate.

Conclusion: Self-nanomicellizing solid dispersions based on RA have great potential as novel oral nano-drug delivery systems for hydrophobic drugs such as Cur.

Citing Articles

Self-assembled nanoparticles of costunolide and glycyrrhizic acid for enhanced ulcerative colitis treatment.

Fu H, Zheng X, Xu K, Zhang Y, Wu M, Xu M BMC Gastroenterol. 2024; 24(1):223.

PMID: 38992591 PMC: 11241987. DOI: 10.1186/s12876-024-03313-9.

Curcumin-Loaded RH60/F127 Mixed Micelles: Characterization, Biopharmaceutical Characters and Anti-Inflammatory Modulation of Airway Inflammation.

Wang X, Wang Y, Tang T, Zhao G, Dong W, Li Q Pharmaceutics. 2023; 15(12).

PMID: 38140051 PMC: 10747166. DOI: 10.3390/pharmaceutics15122710.

Steviol glycosides as an alternative osmotic agent for peritoneal dialysis fluid.

Kopytina V, Pascual-Anton L, Toggweiler N, Arriero-Pais E, Strahl L, Albar-Vizcaino P Front Pharmacol. 2022; 13:868374.

PMID: 36052133 PMC: 9424724. DOI: 10.3389/fphar.2022.868374.

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design.

Goo Y, Sa C, Choi J, Kim M, Kim C, Kim H Int J Nanomedicine. 2021; 16:1245-1259.

PMID: 33633449 PMC: 7901570. DOI: 10.2147/IJN.S298450.

Obstacles against the Marketing of Curcumin as a Drug.

Hassanzadeh K, Buccarello L, Dragotto J, Mohammadi A, Corbo M, Feligioni M Int J Mol Sci. 2020; 21(18).

PMID: 32927725 PMC: 7554750. DOI: 10.3390/ijms21186619.

References

Jung T, KAMM W, Breitenbach A, Kaiserling E, Xiao J, Kissel T . Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake?. Eur J Pharm Biopharm. 2000; 50(1):147-60. DOI: 10.1016/s0939-6411(00)00084-9. View

Weuts I, Kempen D, Six K, Peeters J, Verreck G, Brewster M . Evaluation of different calorimetric methods to determine the glass transition temperature and molecular mobility below T(g) for amorphous drugs. Int J Pharm. 2003; 259(1-2):17-25. DOI: 10.1016/s0378-5173(03)00233-3. View

Avdeef A, Nielsen P, Tsinman O . PAMPA--a drug absorption in vitro model 11. Matching the in vivo unstirred water layer thickness by individual-well stirring in microtitre plates. Eur J Pharm Sci. 2004; 22(5):365-74. DOI: 10.1016/j.ejps.2004.04.009. View

Feng B, Mills J, Davidson R, Mireles R, Janiszewski J, Troutman M . In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab Dispos. 2007; 36(2):268-75. DOI: 10.1124/dmd.107.017434. View

Mensch J, Melis A, Mackie C, Verreck G, Brewster M, Augustijns P . Evaluation of various PAMPA models to identify the most discriminating method for the prediction of BBB permeability. Eur J Pharm Biopharm. 2010; 74(3):495-502. DOI: 10.1016/j.ejpb.2010.01.003. View

Uchiyama H, Tozuka Y, Imono M, Takeuchi H . Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability. Eur J Pharm Biopharm. 2010; 76(2):238-44. DOI: 10.1016/j.ejpb.2010.07.006. View

Zhang F, Koh G, Jeansonne D, Hollingsworth J, Russo P, Vicente G . A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity. J Pharm Sci. 2011; 100(7):2778-89. DOI: 10.1002/jps.22512. View

Uchiyama H, Tozuka Y, Nishikawa M, Takeuchi H . Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug. Int J Pharm. 2012; 428(1-2):183-6. DOI: 10.1016/j.ijpharm.2012.01.016. View

Zhang F, Koh G, Hollingsworth J, Russo P, Stout R, Liu Z . Reformulation of etoposide with solubility-enhancing rubusoside. Int J Pharm. 2012; 434(1-2):453-9. DOI: 10.1016/j.ijpharm.2012.06.013. View

10.

Yang R, Zhang S, Kong D, Gao X, Zhao Y, Wang Z . Biodegradable polymer-curcumin conjugate micelles enhance the loading and delivery of low-potency curcumin. Pharm Res. 2012; 29(12):3512-25. DOI: 10.1007/s11095-012-0848-8. View

11.

Jahanshiri Z, Shams-Ghahfarokhi M, Allameh A, Razzaghi-Abyaneh M . Effect of Curcumin on Aspergillus parasiticus Growth and Expression of Major Genes Involved in the Early and Late Stages of Aflatoxin Biosynthesis. Iran J Public Health. 2012; 41(6):72-9. PMC: 3469004. View

12.

Wan Z, Wang J, Wang L, Yang X, Yuan Y . Enhanced physical and oxidative stabilities of soy protein-based emulsions by incorporation of a water-soluble stevioside-resveratrol complex. J Agric Food Chem. 2013; 61(18):4433-40. DOI: 10.1021/jf4003945. View

13.

Saravanan R, Ramachandran V . Modulating efficacy of Rebaudioside A, a diterpenoid on antioxidant and circulatory lipids in experimental diabetic rats. Environ Toxicol Pharmacol. 2013; 36(2):472-483. DOI: 10.1016/j.etap.2013.05.009. View

14.

Chassaing B, Aitken J, Malleshappa M, Vijay-Kumar M . Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014; 104:15.25.1-15.25.14. PMC: 3980572. DOI: 10.1002/0471142735.im1525s104. View

15.

Agrawal U, Sharma R, Gupta M, Vyas S . Is nanotechnology a boon for oral drug delivery?. Drug Discov Today. 2014; 19(10):1530-46. DOI: 10.1016/j.drudis.2014.04.011. View

16.

Onoue S, Suzuki H, Kojo Y, Matsunaga S, Sato H, Mizumoto T . Self-micellizing solid dispersion of cyclosporine A with improved dissolution and oral bioavailability. Eur J Pharm Sci. 2014; 62:16-22. DOI: 10.1016/j.ejps.2014.05.006. View

17.

Wang H, Cui Y, Fu Q, Deng B, Li G, Yang J . A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Dev Ind Pharm. 2014; 41(10):1693-703. DOI: 10.3109/03639045.2014.991402. View

18.

Ge W, Li D, Chen M, Wang X, Liu S, Sun R . Characterization and antioxidant activity of β-carotene loaded chitosan-graft-poly(lactide) nanomicelles. Carbohydr Polym. 2014; 117:169-176. DOI: 10.1016/j.carbpol.2014.09.056. View

19.

Lean Q, Eri R, Fitton J, Patel R, Gueven N . Fucoidan Extracts Ameliorate Acute Colitis. PLoS One. 2015; 10(6):e0128453. PMC: 4471193. DOI: 10.1371/journal.pone.0128453. View

20.

Xiao B, Si X, Zhang M, Merlin D . Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy. Colloids Surf B Biointerfaces. 2015; 135:379-385. PMC: 4695233. DOI: 10.1016/j.colsurfb.2015.07.081. View