Optimization of Thiolated Chitosan Nanoparticles for the Enhancement of in Vivo Hypoglycemic Efficacy of Sitagliptin in Streptozotocin-Induced Diabetic Rats

Abstract

Sitagliptin (SGN) is an antidiabetic drug used for treatment of diabetes mellitus type II. The objectives of this study were to formulate SGN in form of thiolated chitosan (TC) nanoparticles to enhance the mucoadhesion properties of SGN to the gastrointestinal tract, prolong drug release, decrease side effects, and enhance patient compliance. Seventeen batches of SGN-TC nanoparticles were designed by Box-Behnken design and prepared using the ionic gelation method using tripolyphosphate (TPP) as crosslinking agent. The prepared formulations were evaluated for particle size, entrapment efficiency %, and in vitro drug release. Based on the results of optimization, three formulations (F1–F3) were prepared with different drug polymer ratios (1:1, 1:2, and 1:3). The mucoadhesion study and in vivo hypoglycemic activity of three formulations were evaluated in comparison to free SGN in streptozotocin (STZ)-induced diabetic rats. The seventeen SGN-TC nanoparticles showed small particle sizes, high entrapment efficiency, and prolonged drug release. The concentration of TC polymers had highest effect on these responses. The percentage of SGN–TC nanoparticles adhered to tissue was increased and the release was prolonged as the concentration of TC polymer increased (F3 > F2 > F1). The hypoglycemic effect of SGN-TC nanoparticles was significantly higher than resulted by free SGN. It was concluded that TC nanoparticles had the ability to enhance the mucoadhesion properties of SGN and prolong the drug release. SGN-TC nanoparticles significantly reduced plasma glucose levels compared to free SGN in STZ-induced diabetic rats.

Fabrication of thiolated chitosan based biodegradable nanoparticles of ticagrelor and their pharmacokinetics

“…A similar pattern for drug release was exhibited by thiolated chitosan NPs for the release of Sitagliptin as reported by Prabahar. 25…”

Thiolated Chitosan Microneedle Patch of Levosulpiride from Fabrication, Characterization to Bioavailability Enhancement Approach

“…The weak peak at 2580.44 cm −1 corresponds to SH, confirming the conjugation between the primary amine of CS and the thioglycolic acid CS-TGA. TC has three characteristic peaks at 1243 cm −1 , corresponding to the vibration of the C-S bond [ 29 , 52 ].…”

Formulation and Characterization of Doxycycline-Loaded Polymeric Nanoparticles for Testing Antitumor/Antiangiogenic Action in Experimental Colon Cancer in Mice

“…The amount of the non-capsulated drug in the supernatant was estimated spectrophotometrically at 269 nm, utilizing an ultraviolet spectrophotometer (Shimadzu, Yokohama, Japan). Different characterizations such as zeta potential (ZP), particle size as well as the polydispersity index (PDI) of the formulated nanoparticles were measured using a Zetasizer (Malvern Instruments Ltd., Malvern, UK) [ 40 , 41 ], while morphology of the surface of the nanoparticles was confirmed using transmission electron microscopy (TEM) (model JTEM-2100, Tokyo, Japan) [ 42 ]. Release of the drug from different trials was carried out using dialysis bag method [ 43 ] at simulated gastric fluid containing 0.1 N HCl and final pH equalsing 1.2 for 2 h and then substituted with phosphate buffer (pH = 6.8) for the next 10 h. Temperature was kept at 37 ± 1 °C, and drug was assayed spectrophotometrically at 269 nm (UV-visible spectrophotometer, Shimadzu, Yokohama, Japan) [ 44 ].…”