Surfactant-Free Glibenclamide Nanoparticles: Formulation, Characterization and Evaluation of Interactions with Biological Barriers

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2021 May 18

PMID 34002324

Citations 3

Authors

Eva C Arrua

Olga Hartwig

Duy-Khiet Ho

Brigitta Loretz

Xabier Murgia

Claudio J Salomon

Claus-Michael Lehr

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer.

Methods: Glibenclamide nanoparticles were obtained by nanoprecipitation and evaluated in terms of drug content, encapsulation efficiency, apparent saturation solubility, drug release profile, solid state and storage stability. The influence of different stirring speed on the particle size, size distribution and zeta potential of the nanoparticles was investigated. The nanoparticle biocompatibility and permeability were analyzed in vitro on Caco-2 cell line (clone HTB-37) and its interaction with mucin was also investigated.

Results: It was found that increasing the molecular weight of polyethylene glycol from 400 to 6000 decreased drug encapsulation, whereas the aqueous solubility and dissolution rate of the drug increased. Particle size of the nanoformulations, with and without polyethylene glycol, were between 140 and 460 nm. Stability studies confirmed that glibenclamide nanoparticles were stable, in terms of particle size, after 120 days at 4°C. In vitro studies indicated minimal interactions of glibenclamide nanoparticles and mucin glycoproteins suggesting favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of these nanoparticles and showed an increased permeation through epithelial cells.

Conclusion: Taking into consideration these findings, polyethylene glycol is a useful polymer for stabilizing these surfactant-free glibenclamide nanoparticles and represent a promising alternative to improve the treatment of non-insulin dependent diabetes.

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References

Coppack S, Lant A, McIntosh C, Rodgers A . Pharmacokinetic and pharmacodynamic studies of glibenclamide in non-insulin dependent diabetes mellitus. Br J Clin Pharmacol. 1990; 29(6):673-84. PMC: 1380169. DOI: 10.1111/j.1365-2125.1990.tb03688.x. View

Lebovitz H . Oral antidiabetic agents: 2004. Med Clin North Am. 2004; 88(4):847-63, ix-x. DOI: 10.1016/j.mcna.2004.05.002. View

Yu L, Amidon G, Polli J, Zhao H, Mehta M, Conner D . Biopharmaceutics classification system: the scientific basis for biowaiver extensions. Pharm Res. 2002; 19(7):921-5. DOI: 10.1023/a:1016473601633. View

Karttunen P, Uusitupa M, Nykanen S, Robinson J, Sipila J . The pharmacokinetics of glibenclamide: a single dose comparison of four preparations in human volunteers. Int J Clin Pharmacol Ther Toxicol. 1985; 23(12):642-6. View

Neugebauer G, BETZIEN G, HRSTKA V, Kaufmann B, von Mollendorff E, Abshagen U . Absolute bioavailability and bioequivalence of glibenclamide (Semi-Euglucon N). Int J Clin Pharmacol Ther Toxicol. 1985; 23(9):453-60. View

Chauhan B, Shimpi S, Paradkar A . Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci. 2005; 26(2):219-30. DOI: 10.1016/j.ejps.2005.06.005. View

Dastmalchi S, Garjani A, Maleki N, Sheikhee G, Baghchevan V, Jafari-Azad P . Enhancing dissolution, serum concentrations and hypoglycemic effect of glibenclamide using solvent deposition technique. J Pharm Pharm Sci. 2005; 8(2):175-81. View

Seedher N, Kanojia M . Co-solvent solubilization of some poorly-soluble antidiabetic drugs. Pharm Dev Technol. 2009; 14(2):185-92. DOI: 10.1080/10837450802498894. View

Klein S, Wempe M, Zoeller T, Buchanan N, Lambert J, Ramsey M . Improving glyburide solubility and dissolution by complexation with hydroxybutenyl-beta-cyclodextrin. J Pharm Pharmacol. 2009; 61(1):23-30. DOI: 10.1211/jpp/61.01.0004. View

10.

Lucio D, Martinez-Oharriz M, Gonzalez-Navarro C, Navarro-Herrera D, Gonzalez-Gaitano G, Radulescu A . Coencapsulation of cyclodextrins into poly(anhydride) nanoparticles to improve the oral administration of glibenclamide. A screening on C. elegans. Colloids Surf B Biointerfaces. 2017; 163:64-72. DOI: 10.1016/j.colsurfb.2017.12.038. View

11.

Savolainen J, Jarvinen K, Taipale H, Jarho P, Loftsson T, Jarvinen T . Co-administration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms. Pharm Res. 1998; 15(11):1696-701. DOI: 10.1023/a:1011900527021. View

12.

Furlanetto S, Cirri M, Piepel G, Mennini N, Mura P . Mixture experiment methods in the development and optimization of microemulsion formulations. J Pharm Biomed Anal. 2011; 55(4):610-7. DOI: 10.1016/j.jpba.2011.01.008. View

13.

Albertini B, Sabatino M, Melegari C, Passerini N . Formulation of spray congealed microparticles with self-emulsifying ability for enhanced glibenclamide dissolution performance. J Microencapsul. 2014; 32(2):181-92. DOI: 10.3109/02652048.2014.985341. View

14.

Sajeev Kumar B, Saraswathi R, Kumar K, Jha S, Venkates D, Dhanaraj S . Development and characterization of lecithin stabilized glibenclamide nanocrystals for enhanced solubility and drug delivery. Drug Deliv. 2013; 21(3):173-84. DOI: 10.3109/10717544.2013.840690. View

15.

Ali H, Hanafy A . Glibenclamide Nanocrystals in a Biodegradable Chitosan Patch for Transdermal Delivery: Engineering, Formulation, and Evaluation. J Pharm Sci. 2016; 106(1):402-410. DOI: 10.1016/j.xphs.2016.10.010. View

16.

Goncalves L, Maestrelli F, Di Cesare Mannelli L, Ghelardini C, Almeida A, Mura P . Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide. Eur J Pharm Biopharm. 2016; 102:41-50. DOI: 10.1016/j.ejpb.2016.02.012. View

17.

Whitehead K, Karr N, Mitragotri S . Safe and effective permeation enhancers for oral drug delivery. Pharm Res. 2007; 25(8):1782-8. DOI: 10.1007/s11095-007-9488-9. View

18.

Seremeta K, Hocht C, Taira C, Cortez Tornello P, Abraham G, Sosnik A . Didanosine-loaded poly(epsilon-caprolactone) microparticles by a coaxial electrohydrodynamic atomization (CEHDA) technique. J Mater Chem B. 2020; 3(1):102-111. DOI: 10.1039/c4tb00664j. View

19.

Dora C, Singh S, Kumar S, Datusalia A, Deep A . Development and characterization of nanoparticles of glibenclamide by solvent displacement method. Acta Pol Pharm. 2010; 67(3):283-90. View

20.

Ho D, Frisch S, Biehl A, Terriac E, De Rossi C, Schwarzkopf K . Farnesylated Glycol Chitosan as a Platform for Drug Delivery: Synthesis, Characterization, and Investigation of Mucus-Particle Interactions. Biomacromolecules. 2018; 19(8):3489-3501. DOI: 10.1021/acs.biomac.8b00795. View