Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Spray-dried Solid Lipid Nanoparticles for Enhancing Berberine Bioavailability via Oral Administration

Author(s): Van Hong Nguyen*, Khoa Nguyen Manh Le and Mai Chau Ngoc Nguyen

Volume 29, Issue 38, 2023

Published on: 13 November, 2023

Page: [3050 - 3059] Pages: 10

DOI: 10.2174/0113816128263982231102062745

Price: $65

Abstract

Background: Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities, especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer's disease. However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations via this route.

Methods: BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN's cytotoxicity for loading BBR was determined with human embryonic kidney cells (HEK293).

Results: Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150% compared to the control sample at 100 μg/mL BBR-unloaded SLNs.

Conclusion: Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.

[1]
Sahibzada MUK, Sadiq A, Faidah HS, et al. Berberine nanoparticles with enhanced in vitro bioavailability: Characterization and antimicrobial activity. Drug Des Devel Ther 2018; 12: 303-12.
[http://dx.doi.org/10.2147/DDDT.S156123] [PMID: 29491706]
[2]
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): 157-67.
[http://dx.doi.org/10.1038/aps.2016.125] [PMID: 27917872]
[3]
Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 2004; 203(2): 127-37.
[http://dx.doi.org/10.1016/j.canlet.2003.09.002] [PMID: 14732220]
[4]
Jin Y, Khadka DB, Cho WJ. Pharmacological effects of berberine and its derivatives: A patent update. Expert Opin Ther Pat 2016; 26(2): 229-43.
[http://dx.doi.org/10.1517/13543776.2016.1118060] [PMID: 26610159]
[5]
Li G, Zhao M, Su X, Song L, Zhao L. Preparation and in vitro-in vivo evaluation of intestinal retention pellets of Berberine chloride to enhance hypoglycemic and lipid-lowing efficacy. Asian J Pharm Sci 2019; 14(5): 559-68.
[6]
Sailor G, Ramani VD, Shah N et al. Design of experiment approach based formulation optimization of berberine loaded solid lipid nanoparticle for antihyperlipidemic activity. Indian J Pharm Sci 2021; 83(2): 204-18.
[7]
Lohan S, Raza K, Mehta SK, Bhatti GK, Saini S, Singh B. Anti-Alzheimer’s potential of berberine using surface decorated multi-walled carbon nanotubes: A preclinical evidence. Int J Pharm 2017; 530(1-2): 263-78.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.080] [PMID: 28774853]
[8]
Cai Y, Xin Q, Lu J, et al. A new therapeutic candidate for cardiovascular diseases: Berberine. Front Pharmacol 2021; 12: 631100.
[http://dx.doi.org/10.3389/fphar.2021.631100] [PMID: 33815112]
[9]
Yu J-L, Wang BW, Zhang HL et al. Therapeutic potential of berberine for osteoporosis and its underlying mechanisms: A bioinformatics, network pharmacology, molecular dynamics simulation study. Nat Prod Commun 2022; 17(5): 1934578X221094913.
[http://dx.doi.org/10.1177/1934578X221094913]
[10]
Tabeshpour J, Imenshahidi M, Hosseinzadeh H. A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci 2017; 20(5): 557-68.
[PMID: 28656091]
[11]
Wang L, Peng LY, Wei GH, Ge H. Therapeutic effects of berberine capsule on patients with mild hyperlipidemia. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 2016; 36(6): 681-4.
[PMID: 27491226]
[12]
Suadoni MT, Atherton I. Berberine for the treatment of hypertension: A systematic review. Complement Ther Clin Pract 2021; 42: 101287.
[http://dx.doi.org/10.1016/j.ctcp.2020.101287] [PMID: 33461163]
[13]
Chang W, Chen L, Hatch GM. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochem Cell Biol 2015; 93(5): 479-86.
[http://dx.doi.org/10.1139/bcb-2014-0107] [PMID: 25607236]
[14]
Wang L, Kong H, Jin M, et al. Synthesis of disaccharide modified berberine derivatives and their anti-diabetic investigation in zebrafish using a fluorescence-based technology. Org Biomol Chem 2020; 18(18): 3563-74.
[http://dx.doi.org/10.1039/D0OB00327A] [PMID: 32347284]
[15]
Spinozzi S, Colliva C, Camborata C, et al. Berberine and its metabolites: relationship between physicochemical properties and plasma levels after administration to human subjects. J Nat Prod 2014; 77(4): 766-72.
[http://dx.doi.org/10.1021/np400607k] [PMID: 24593257]
[16]
Liu YT, Hao HP, Xie HG, et al. Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metab Dispos 2010; 38(10): 1779-84.
[http://dx.doi.org/10.1124/dmd.110.033936] [PMID: 20634337]
[17]
Lu Q, Dun J, Chen JM, Liu S, Sun CC. Improving solid-state properties of berberine chloride through forming a salt cocrystal with citric acid. Int J Pharm 2019; 554: 14-20.
[http://dx.doi.org/10.1016/j.ijpharm.2018.10.062] [PMID: 30385378]
[18]
Sun J, Bao H, Peng Y, et al. Improvement of intestinal transport, absorption and anti-diabetic efficacy of berberine by using Gelucire44/14: In vitro, in situ and in vivo studies. Int J Pharm 2018; 544(1): 46-54.
[http://dx.doi.org/10.1016/j.ijpharm.2018.04.014] [PMID: 29654898]
[19]
Shi C, Tong Q, Fang J, Wang C, Wu J, Wang W. Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine. Eur J Pharm Sci 2015; 74: 11-7.
[http://dx.doi.org/10.1016/j.ejps.2015.04.001] [PMID: 25861719]
[20]
Zhou Y, Liu S, Ming J, Li Y, Deng M, He B. Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture. Drug Dev Ind Pharm 2017; 43(10): 1703-14.
[http://dx.doi.org/10.1080/03639045.2017.1339076] [PMID: 28585864]
[21]
Yu F, Ao M, Zheng X, et al. PEG–lipid–PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency. Drug Deliv 2017; 24(1): 825-33.
[http://dx.doi.org/10.1080/10717544.2017.1321062] [PMID: 28509588]
[22]
Jia J, Zhang K, Zhou X, et al. Berberine-loaded solid proliposomes prepared using solution enhanced dispersion by supercritical CO2: Sustained release and bioavailability enhancement. J Drug Deliv Sci Technol 2019; 51: 356-63.
[http://dx.doi.org/10.1016/j.jddst.2019.03.021]
[23]
Phan TNQ, Shahzadi I, Bernkop-Schnürch A. Hydrophobic ion- pairs and lipid-based nanocarrier systems: The perfect match for delivery of BCS class 3 drugs. J Control Release 2019; 304: 146-55.
[http://dx.doi.org/10.1016/j.jconrel.2019.05.011] [PMID: 31075345]
[24]
Souto EB, Doktorovova S, Zielinska A, Silva AM. Key production parameters for the development of solid lipid nanoparticles by high shear homogenization. Pharm Dev Technol 2019; 24(9): 1181-5.
[http://dx.doi.org/10.1080/10837450.2019.1647235] [PMID: 31354002]
[25]
Santos D. Spray drying: an overview. In: Pignatello R, Ed. Biomaterials-Physics and Chemistry-New Edition. UK: InTech 2018; pp. 9-35.
[http://dx.doi.org/10.5772/intechopen.72247]
[26]
Salminen H, Ankenbrand J, Zeeb B, et al. Influence of spray drying on the stability of food-grade solid lipid nanoparticles. Food Res Int 2019; 119: 741-50.
[http://dx.doi.org/10.1016/j.foodres.2018.10.056] [PMID: 30884711]
[27]
Van NH. Nanostructured lipid carriers and their potential applications for versatile drug delivery via oral administration. OpenNano. 2022; p. 100064.
[28]
Sakellari GI. Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active. Food Hydrocolloids Health 2021; 1: 100024.
[29]
Vieira R, Severino P, Nalone LA, et al. Sucupira oil-loaded nanostructured lipid carriers (NLC): Lipid screening, factorial design, release profile, and cytotoxicity. Molecules 2020; 25(3): 685.
[http://dx.doi.org/10.3390/molecules25030685] [PMID: 32041134]
[30]
Musielak E, Feliczak-Guzik A, Nowak I. Optimization of the conditions of solid lipid nanoparticles (SLN) synthesis. Molecules 2022; 27(7): 2202.
[http://dx.doi.org/10.3390/molecules27072202] [PMID: 35408600]
[31]
Kumar R, Singh A, Garg N, Siril PF. Solid lipid nanoparticles for the controlled delivery of poorly water soluble non-steroidal anti-inflammatory drugs. Ultrason Sonochem 2018; 40(Pt A): 686-96.
[http://dx.doi.org/10.1016/j.ultsonch.2017.08.018] [PMID: 28946474]
[32]
Health, M.o. Vietnamese Pharmacopoeia. (5 ed.). 2017; 1.
[33]
Mura P, Maestrelli F, D’Ambrosio M, Luceri C, Cirri M. Evaluation and comparison of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as vectors to develop hydrochlorothiazide effective and safe pediatric oral liquid formulations. Pharmaceutics 2021; 13(4): 437.
[http://dx.doi.org/10.3390/pharmaceutics13040437] [PMID: 33804945]
[34]
Kim JH, Baek JS, Park JK, et al. Development of Houttuynia cordata extract-loaded solid lipid nanoparticles for oral delivery: High drug loading efficiency and controlled release. Molecules 2017; 22(12): 2215.
[http://dx.doi.org/10.3390/molecules22122215] [PMID: 29236057]
[35]
Paul J. Handbook of Pharmaceutical Excipients. (8th Revised ed..), Pharmaceutical Press 2017.
[36]
Yeo S, Kim MJ, Shim YK, Yoon I, Lee WK. Solid lipid nanoparticles of curcumin designed for enhanced bioavailability and anticancer efficiency. ACS Omega 2022; 7(40): 35875-84.
[http://dx.doi.org/10.1021/acsomega.2c04407] [PMID: 36249382]
[37]
Deng J, Wu Z, Zhao Z, et al. Berberine-loaded nanostructured lipid carriers enhance the treatment of ulcerative colitis. Int J Nanomedicine 2020; 15: 3937-51.
[http://dx.doi.org/10.2147/IJN.S247406] [PMID: 32581538]
[38]
Nguyen MC-N. Solid Lipid Nanoparticles Containing Berberine by Spray-Drying Method. International Conference on the Development of Biomedical Engineering in Vietnam. Springer. 2020.
[39]
Wang L, Li H, Wang S, et al. Enhancing the antitumor activity of berberine hydrochloride by solid lipid nanoparticle encapsulation. AAPS PharmSciTech 2014; 15(4): 834-44.
[http://dx.doi.org/10.1208/s12249-014-0112-0] [PMID: 24696391]
[40]
Ali ME, Lamprecht A. Spray freeze drying as an alternative technique for lyophilization of polymeric and lipid-based nanoparticles. Int J Pharm 2017; 516(1-2): 170-7.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.023] [PMID: 27845211]
[41]
Wang T, Hu Q, Zhou M, Xue J, Luo Y. Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology. Int J Pharm 2016; 511(1): 219-22.
[http://dx.doi.org/10.1016/j.ijpharm.2016.07.005] [PMID: 27395801]
[42]
Vasconcelos T, Prezotti F, Araújo F, et al. Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int J Pharm 2021; 595: 120245.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120245] [PMID: 33484925]
[43]
Sakayori N, Kimura R, Osumi N. Impact of lipid nutrition on neural stem/progenitor cells. Stem Cells Int 2023; 2013.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy