Berberine Nanoparticles with Enhanced in Vitro Bioavailability: Characterization and Antimicrobial Activity

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2018 Mar 2

PMID 29491706

Citations 45

Authors

Muhammad Umar Khayam Sahibzada

Abdul Sadiq

Hani S Faidah

Muhammad Khurram

Muhammad Usman Amin

Abdul Haseeb

Maria Kakar

Affiliations

Soon will be listed here.

Abstract

Background: Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine.

Methods: Semi-crystalline nanoparticles (NPs) of 90-110 nm diameter for APSP and 65-75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity.

Results: The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form.

Conclusion: Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

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References

Yesilada E, Kupeli E . Berberis crataegina DC. root exhibits potent anti-inflammatory, analgesic and febrifuge effects in mice and rats. J Ethnopharmacol. 2002; 79(2):237-48. DOI: 10.1016/s0378-8741(01)00387-7. View

Kupeli E, Kosar M, Yesilada E, Husnu K, Baser C . A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sci. 2002; 72(6):645-57. DOI: 10.1016/s0024-3205(02)02200-2. View

Pattekari P, Zheng Z, Zhang X, Levchenko T, Torchilin V, Lvov Y . Top-down and bottom-up approaches in production of aqueous nanocolloids of low solubility drug paclitaxel. Phys Chem Chem Phys. 2011; 13(19):9014-9. PMC: 4378541. DOI: 10.1039/c0cp02549f. View

Hayashi K, Minoda K, Nagaoka Y, Hayashi T, Uesato S . Antiviral activity of berberine and related compounds against human cytomegalovirus. Bioorg Med Chem Lett. 2007; 17(6):1562-4. DOI: 10.1016/j.bmcl.2006.12.085. View

Horn D, Rieger J . Organic Nanoparticles in the Aqueous Phase-Theory, Experiment, and Use. Angew Chem Int Ed Engl. 2002; 40(23):4330-4361. DOI: 10.1002/1521-3773(20011203)40:23<4330::aid-anie4330>3.0.co;2-w. View

Tsai P, Tsai T . Hepatobiliary excretion of berberine. Drug Metab Dispos. 2004; 32(4):405-12. DOI: 10.1124/dmd.32.4.405. View

Taylor C, Winter D, Skelly M, ODonoghue D, OSullivan G, Harvey B . Berberine inhibits ion transport in human colonic epithelia. Eur J Pharmacol. 1999; 368(1):111-8. DOI: 10.1016/s0014-2999(99)00023-0. View

Kakran M, Sahoo N, Li L, Judeh Z, Wang Y, Chong K . Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. Int J Pharm. 2009; 383(1-2):285-92. DOI: 10.1016/j.ijpharm.2009.09.030. View

Murdande S, Pikal M, Shanker R, Bogner R . Solubility advantage of amorphous pharmaceuticals: II. Application of quantitative thermodynamic relationships for prediction of solubility enhancement in structurally diverse insoluble pharmaceuticals. Pharm Res. 2010; 27(12):2704-14. DOI: 10.1007/s11095-010-0269-5. View

10.

Pan G, Huang Z, Wang G, Fawcett J, Liu X, Zhao X . The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med. 2003; 69(7):632-6. DOI: 10.1055/s-2003-41121. View

11.

Murdande S, Pikal M, Shanker R, Bogner R . Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis. J Pharm Sci. 2009; 99(3):1254-64. DOI: 10.1002/jps.21903. View

12.

Cheng Z, Chen A, Wu F, Sheng L, Zhang H, Gu M . 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Bioorg Med Chem. 2010; 18(16):5915-24. DOI: 10.1016/j.bmc.2010.06.085. View

13.

. Increase in action potential duration and inhibition of the delayed rectifier outward current IK by berberine in cat ventricular myocytes. Br J Pharmacol. 1996; 117(7):1427-34. PMC: 1909453. DOI: 10.1111/j.1476-5381.1996.tb15302.x. View

14.

Park K, Kang K, Kim J, Adams D, Johng T, Paik Y . Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans. J Antimicrob Chemother. 1999; 43(5):667-74. DOI: 10.1093/jac/43.5.667. View

15.

Keck C, Muller R . Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2005; 62(1):3-16. DOI: 10.1016/j.ejpb.2005.05.009. View

16.

Hancock B, Parks M . What is the true solubility advantage for amorphous pharmaceuticals?. Pharm Res. 2000; 17(4):397-404. DOI: 10.1023/a:1007516718048. View

17.

Teodoro J, Duarte F, Gomes A, Varela A, Peixoto F, Rolo A . Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation. Mitochondrion. 2013; 13(6):637-46. DOI: 10.1016/j.mito.2013.09.002. View

18.

Mullauer F, van Bloois L, Daalhuisen J, Ten Brink M, Storm G, Medema J . Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity. Anticancer Drugs. 2011; 22(3):223-33. DOI: 10.1097/CAD.0b013e3283421035. View

19.

Hua W, Ding L, Chen Y, Gong B, He J, Xu G . Determination of berberine in human plasma by liquid chromatography-electrospray ionization-mass spectrometry. J Pharm Biomed Anal. 2007; 44(4):931-7. DOI: 10.1016/j.jpba.2007.03.022. View

20.

Zhaojie M, Ming Z, Shengnan W, Xiaojia B, Hatch G, Jingkai G . Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability. Int J Pharm. 2014; 467(1-2):50-9. DOI: 10.1016/j.ijpharm.2014.03.017. View