Development and Characterization of a Glimepiride-Loaded Gelatin-Coated Mesoporous Hollow Silica Nanoparticle Formulation and Evaluation of Its Hypoglycemic Effect on Type-2 Diabetes Model Rats

Abstract

In this study, we prepared gelatin-coated mesoporous hollow silica nanospheres (GSN) as a drug carrier to improve the water solubility and regulate the release rate of glimepiride (GLM). GLM was loaded into GSN by an absorption method, and drugloaded samples (GLM-GSN) were characterized by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). Cellular uptake and in vivo intestinal uptake experiments were performed in rats. In addition, the studies of in-vitro drug dissolution, pharmacokinetics, and pharmacodynamic experiments also were performed. GLM-GSN showed excellent drug loading (39.7%-0.7%) and sustained GLM release. The state of GLM in GSN was amorphous according to DSC and XRD results. Cellular uptake and in vivo intestinal uptake experiments indicated that GSN could be effectively absorbed, and an MTT experiment demonstrated that GSN had good biocompatibility. Furthermore, the GLM-GSN had a higher bioavailability in pharmacokinetics experiments and a prominent hypoglycemic effect on type-2 diabetes model rats in pharmacodynamic experiments. This study clearly shows that GSN is a promising platform for delivering GLM for the treatment of type-2 diabetes.

Natural Biopolymers as Smart Coating Materials of Mesoporous Silica Nanoparticles for Drug Delivery

“…This functional diversity allows it to be modified by using nanoparticles and biomolecules. In addition, gelatin is an extracellular matrix protein which allows it to be applied in wound dressings, drug delivery, and gene transfection [ 252 , 253 , 254 ]. It presents desirable features, such as natural origin, low-cost, low-toxicity, biodegradability, and non-immunogenicity, although it shows poor stability in aqueous solutions [ 255 ].…”

The effect of size, morphology and surface properties of mesoporous silica nanoparticles on pharmacokinetic aspects and potential toxicity concerns

“…Glimepiride-GSNs showed 40% drug release at 1 h and more than 90% during 24 h. In addition, this study revealed that the T max , mean residence time (MRT), and 24-h area under the curve (AUC 0-24h ) values in glimepiride-GSNs were significantly higher than the commercially available product counterparts. Moreover, the bioavailability of glimepiride was enhanced after incorporation into the GSNs and also lead to higher cellular and intestinal mucosal uptake (Yu et al, 2020).…”

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

“…These formulations were able to prolong the encapsulated drug release up to 60 h and the treatment of cell cultures by obtained formulations showed good viability of MRC-5 fibroblast cells and suppression of HeLa cells [238]. The authors of [239] designed gelatin-coated mesoporous hollow silica nanospheres and used them for glimepiride encapsulation. Formulations were characterized by high drug loading (40%) and more than a 2-fold higher duration of hypoglycemic effect in comparison with commercially available formulations, which allows researchers to recommend them as perspective candidates for the treatment of type 2 diabetes.…”