Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide

Abstract

a b s t r a c tA solid lipid nanoparticle (SLN) formulation was developed with the aim of improving the oral bioavailability and the therapeutic effectiveness of glibenclamide (GLI), a poorly water-soluble drug used in the treatment of type 2 diabetes. The SLN was prepared using different lipid components (Precirol Ò and Compritol Ò) and preparation procedures. Precirol-based SLN, obtained with the emulsion of solvent evaporation technique gave the best results and was selected for drug loading. Addition of lecithin to the SLN core or PEG coating was effective in increasing the nanoparticles stability in simulated gastric solution. Both such formulations were stable after one month storage at 5 ± 3°C, exhibited the absence of in vitro cytotoxicity, and presented a similar in vitro prolonged-release, reaching 100% release after 24 h. The lecithin-containing GLI-loaded SLN formulation, selected for in vivo studies in virtue of its higher EE% than the PEG-coated formulation (70.3% vs 19.6%), showed a significantly stronger hypoglycemic effect with respect to the drug alone, in terms of both shorter onset time and longer duration of the effect. These positive results indicated that the proposed SLN approach was successful in improving GLI oral bioavailability, confirming its potential as an effective delivery system for a suitable therapy of diabetes.

<p>Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study</p>

“…Mainly, the nanoscale dimensions of the particles combined with the almost molecular dispersion of the drug molecules into the lipid carrier and the presence of surfactants, which strongly increased the drug gastrointestinal solubilization, and the in vivo absorption. 51 Another interpretation was that due to their small particle size, SLNs might exhibit bio-adhesion to the gastrointestinal tract wall or enter the inter-villar spaces thus increasing their residence time in the gastrointestinal tract. This increased adhesion would result in enhanced bioavailability.…”

“…This increased adhesion would result in enhanced bioavailability. 51,52 Time to reach maximum plasma concentration (T max ) is a measurement for the rate of drug absorption. Raw GLZ powder showed erratic absorption, with high intersubject variation regarding T max ranging from as low as half an hour, up to 4 h. Such behavior was already reported, and could be related to its early dissolution in the stomach leading to more variability in the absorption in the intestine.…”

Calcium alginate microspheres containing metformin hydrochloride niosomes and chitosomes aimed for oral therapy of type 2 diabetes mellitus

“…Different kinds of colloidal carriers, such as lipid and polymeric nanoparticles, and different kinds of vesicular systems, have been investigated as a strategy to improve drug bioavailability, control its release rate and/or obtain site-specific drug targeting (Barratt 2003;Mishra et al, 2010;Gonçalves et al, 2016). Among these, vesicular carriers like liposomes are of particular interest, due to their ability to easily encapsulate both hydrophobic and hydrophilic drugs, together with their biocompatibility, biodegradability and very low toxicity (Jain et al, 2014;Maestrelli et al, 2016).…”

Comparison of intestinal permeability of nebivolol hydrochloride loaded solid lipid nanoparticles with commercial nebivolol tablet

“…There are several possible mechanisms to explain the enhanced permeability/bioavailability of drugs given in nano-lipid carriers; such as i) maintaining a solubilized state of the drugs in the GI tract, ii) formation of mixed micelles, iii) promoting the secretion of endogenous phospholipids and bile salts [30]. These mechanisms might be used to explain the enhanced absorption obtained with NBV loaded SLNs.…”