Preparation and Characterization of Berberine loaded Micelle Formulations with Approach to Oral Drug Delivery

Document Type : Original Article

Authors

1 Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Pharmaceutical Nanotechnology, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Berberine (BBR) is a quaternary ammonium salt that possesses plentiful therapeutics properties. But notwithstanding the positive points, it has two negative points: poor aqueous solubility and permeability. These properties are important for achieving good bioavailability and therapeutic effect. Lately nano formulations developed to overcome these challenges through drug encapsulation. The aim of this study was preparation of nano formulations based on surfactant to achieve the best formulation with good characteristics. In this research, nano micellar formulations were prepared by thin film hydration method using poly sorbate 20 as surfactant and BBR as drug to get the good formulation based on high encapsulation efficiency (EE). Then nano micelles were characterized by particle size and polydispersity index (PDI) by DLS, drug encapsulation by UV-Vis spectrophotometer and drug release behavior in simulated gastro fluid (SGF) and simulated intestinal fluid (SIF). BBR successfully was encapsulated within micelles by thin film hydration method. DLS analysis showed average size of nano micelle samples between 9.247 and 18.46 nm, PDI was about 0.271, with maximum percentage of drug encapsulation of 78%. Also fluctuation of drug release was very low in elementary time points in SGF and SIF, and it was approximately sustained release profile. These results showed to achieve a good formulation and in order to have better drug delivery, physical attributes including the size distribution, PDI, and EE should be controlled. Our findings may be benefactress for different applications in variety research fields of pharmaceutical industry. 

Keywords

References

1. Homayun B, Lin X, Choi HJ. Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics. 2019 Mar 19;11(3):129. doi: 10.3390/pharmaceutics11030129.
2. Ma S, Wang L, Huang X, Wang X, Chen S, Shi W, Qiao X, Jiang Y, Tang L, Xu Y, Li Y. Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus. Microb Cell Fact. 2018 Feb 9;17(1):20. doi: 10.1186/s12934-018-0861-7.
3. Kwon K, Daniell H. Oral delivery of protein drugs bioencapsulated in plant cells. Mol Ther. 2016; 24: 1342-50.
4. Pund S, Borade G, Rasve G. Improvement of anti-inflammatory and anti-angiogenic activity of berberine by novel rapid dissolving nanoemulsifying technique. Phytomedicine. 2014 Feb 15;21(3):307-14. doi: 10.1016/j.phymed.2013.09.013.
5. Singh N, Sharma B. Toxicological Effects of Berberine and Sanguinarine. Front Mol Biosci. 2018 Mar 19;5:21. doi: 10.3389/fmolb.2018.00021.
6. Fan D, Liu L, Wu Z, Cao M. Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential. Curr Neuropharmacol. 2019;17(6):563-579. doi:10.2174/1570159X16666180419141613
7. Li Z, Geng YN, Jiang JD, Kong WJ. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med. 2014;2014:289264. doi: 10.1155/2014/289264.
8. Xu JH, Liu XZ, Pan W, Zou DJ. Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol Med Rep. 2017;15(5):2765-2787. doi:10.3892/mmr.2017.6321
9. Zou K, Li Z, Zhang Y, et al. Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol Sin. 2017;38(2):157-167. doi:10.1038/aps.2016.125
10. Neag MA, Mocan A, Echeverría J, Pop RM, Bocsan CI, Crişan G, Buzoianu AD. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol. 2018 Aug 21;9:557. doi: 10.3389/fphar.2018.00557.
11. Yuan NN, Cai CZ, Wu MY, Su HX, Li M, Lu JH. Neuroprotective effects of berberine in animal models of Alzheimer's disease: a systematic review of pre-clinical studies. BMC Complement Altern Med. 2019 May 23;19(1):109. doi: 10.1186/s12906-019-2510-z.
12. Hasanein P, Ghafari-Vahed M, Khodadadi I. Effects of isoquinoline alkaloid berberine on lipid peroxidation, antioxidant defense system, and liver damage induced by lead acetate in rats. Redox Rep. 2017 Jan;22(1):42-50. doi: 10.1080/13510002.2016.1140406.
13. Sahibzada MUK, Sadiq A, Faidah HS, Khurram M, Amin MU, Haseeb A, Kakar M. Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity. Drug Des Devel Ther. 2018 Feb 14;12:303-312. doi: 10.2147/DDDT.S156123.
14. Cui HX, Hu YN, Li JW, Yuan K, Guo Y. Preparation and Evaluation of Antidiabetic Agents of Berberine Organic Acid Salts for Enhancing the Bioavailability. Molecules. 2018 Dec 28;24(1):103. doi: 10.3390/molecules24010103.
15. Liu CS, Zheng YR, Zhang YF, Long XY. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. 2016 Mar;109:274-82. doi: 10.1016/j.fitote.2016.02.001.
16. Kumar A, Ekavali, Chopra K, Mukherjee M, Pottabathini R, Dhull DK. Current knowledge and pharmacological profile of berberine: An update. Eur J Pharmacol. 2015 Aug 15;761:288-97. doi: 10.1016/j.ejphar.2015.05.068.
17. Ye M, Fu S, Pi R, He F. Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research. J Pharm Pharmacol. 2009 Jul;61(7):831-7. doi: 10.1211/jpp/61.07.0001.
18. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018 Sep 19;16(1):71. doi: 10.1186/s12951-018-0392-8.
19. Lu Y, Yue Z, Xie J, Wang W, Zhu H, Zhang E, Cao Z. Micelles with ultralow critical micelle concentration as carriers for drug delivery. Nat Biomed Eng. 2018 May;2(5):318-325. doi: 10.1038/s41551-018-0234-x.
20. Long JA, Rankin BM, Ben-Amotz D. Micelle Structure and Hydrophobic Hydration. J Am Chem Soc. 2015 Aug 26;137(33):10809-15. doi: 10.1021/jacs.5b06655.
21. Santos M, Tavares F, Biscaia E. molecular thermodynamics of micellization: micelle size distributions and geometry transitions. Braz J Chem Eng. 2016; 33(3): 515-523. doi.org/10.1590/0104-6632.20160333s20150129.
22. Lu Y, Zhang E, Yang J, Cao Z. Strategies to improve micelle stability for drug delivery. Nano Res. 2018 Oct;11(10):4985-4998. doi: 10.1007/s12274-018-2152-3.
23. Yang T, Li W, Duan X, et al. Preparation of Two Types of Polymeric Micelles Based on Poly(β-L-Malic Acid) for Antitumor Drug Delivery. PLoS One. 2016;11(9):e0162607. Published 2016 Sep 20. doi:10.1371/journal.pone.0162607
24. Hanafy NAN, El-Kemary M, Leporatti S. Micelles Structure Development as a Strategy to Improve Smart Cancer Therapy. Cancers (Basel). 2018;10(7):238. Published 2018 Jul 20. doi:10.3390/cancers10070238
25. Mandal A, Bisht R, Rupental L, Mitra A. Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies. J Control Release. 2017; 248: 96–116, doi: 10.1016/j.jconrel.2017.01.012.
26. Adrion AC, Nakamura J, Shea D, Aitken MD. Screening Nonionic Surfactants for Enhanced Biodegradation of Polycyclic Aromatic Hydrocarbons Remaining in Soil After Conventional Biological Treatment. Environ Sci Technol. 2016 Apr 5;50(7):3838-45. doi: 10.1021/acs.est.5b05243.
27. Lv S, Wu Y, Cai K, He H, Li Y, Lan M, Chen X, Cheng J, Yin L. High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles Driven by Donor-Receptor Coordination Interactions. J Am Chem Soc. 2018 Jan 31;140(4):1235-1238. doi: 10.1021/jacs.7b12776.
28. Szymczyk K, Szaniawska M, Taraba A. Micellar Parameters of Aqueous Solutions of Tween 20 and 60 at Different Temperatures: Volumetric and Viscometric Study. Colloids Interfaces. 2018; 2: 34, doi:10.3390/colloids2030034.
29. Ai X, Zhong L, Niu H, He Zh. Thin-film hydration preparation method and stability test of DOX-loaded disulfide-linked polyethylene glycol 5000-lysine-di-tocopherol succinate nanomicelles. Asian J Pharm Sci. 2014; 9(5): 244-250, doi.org/10.1080/10837450.2017.1330345.
30. Rojsanga P, Gritsanapan W, Suntornsuk L. Determination of berberine content in the stem extracts of Coscinium fenestratum by TLC densitometry. Med Princ Pract. 2006;15(5):373-8. doi: 10.1159/000094272. PMID: 16888396.
31. Ebrahimi Nik M, Malaekeh-Nikouei B, Amin M, Hatamipour M, Teymouri M, Sadeghnia H.R, et al. Liposomal formulation of Galbanic acid improved therapeutic efcacy of pegylated liposomal Doxorubicin in mouse colon carcinoma. Sci Rep. 2019;9:9527. doi.org/10.1038/s41598-019-45974-7.
32. Hatamipour M, Sahebkar A, Alavizadeh SH, Dorri M, Jaafari MR. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids. Iran J Basic Med Sci. 2019 Mar;22(3):282-289. doi: 10.22038/ijbms.2019.32873.7852.
33. Deepak Sh, Dipika M, Gilphy Ph, Ravish R, Shanu B, Manisha S, et al. Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation. BioMed Res Inter. 2014, 3:156010. doi: 10.1155/2014/156010.
34. Bahari L.A. Hamishehkar H. The impact of variables on particle size of solid lipid nanoparticles and nanostructured lipid carriers; a comparative literature review. Adv Pharm Bull. 2016; 6 (2): 143. doi: 10.15171/apb.2016.021.
35. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018 May 18;10(2):57. doi: 10.3390/pharmaceutics10020057.
36. Mantha S, Qi Sh, Barz M, Schemid F. How ill-defined constituents produce well-defined nanoparticles: Effect of polymer dispersity on the uniformity of copolymeric micelles. 2019;3(2), doi.org/10.1103/PhysRevMaterials.3.026002.
37. Maherani B, Wattraint O. Liposomal structure: A comparative study on light scattering and chromatography techniques. J Dispers Sci Technol. 2017;38:1633-9, doi.org/10.1080/01932691.2016.1269651.
38. International Standard ISO22412 Particle Size Analysis-Dynamic Light Scattering, International Organisation for Standardisation (ISO) 2008.
39. Ford J.L: Particle Size Analysis in Pharmaceutics and Other Industries: Theory and Practice. Ellis Horwood, England, 1993.
Trends in Pharmaceutical Sciences
Volume 6, Issue 4
December 2020
Pages 255-262

Files

Share

How to cite

Statistics