Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics

Abstract

Sitagliptin (MK–0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

HPMC- and PLGA-Based Nanoparticles for the Mucoadhesive Delivery of Sitagliptin: Optimization and In Vivo Evaluation in Rats

“…The prepared nanoparticles showed a narrow particle size distribution with an average particle size of 448.8 nm (Figure 7). The particle size observed here is also comparable with the earlier studies [11,12]. Narrow size distribution will help to maintain constant plasma levels within the therapeutic window for a longer time and will decrease incidents of toxicity or underexposure, which is vital for any dosage form.…”

“…Spray-dried formulations require a one-step process to produce dried particles in comparison to conventional techniques. Spray-drying resulted in an irregular (shriveled) shape of the particles, which is moderately different from our earlier studies, where the polymer used was albumin or chitosan [11,12]. This caused shriveled shapes because sprayed drops came in contact with the hot air in the drying chamber, which resulted in the particle swelling, shrinking, or twisting.…”

“…Indeed, such a retention profile is ideal for the prolonged release of sitagliptin by extending the residence time of nanoparticles in the GIT. Moreover, the values observed here also signify that the combination of HPMC and PLGA nanoparticles can provide greater drug retention than the chitosan nanoparticles [12]. Alternatively, the percentage of drug retained in the GIT drastically decreased and was significantly low (p < 0.05) when administered as a suspension.…”

“…The literature signifies that studies have also been carried out to enhance the therapeutic efficacy of various drugs by formulating mucoadhesive nanoparticles intended for oral therapy [8][9][10]. During the past few decades, various sitagliptin-loaded polymeric nano formulations for oral drug delivery have been developed to enhance bioavailability [2,11,12].…”

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

“…The mucoadhesive delivery system has improved the pharmacokinetic and pharmacological properties of drugs, which can be advantageous when used in the treatment of acute and chronic diseases [1]. The mucoadhesive drug delivery carrier has many potential advantages, like improved bioavailability of drugs, due to increasing the residence time in the mucosa, a lower frequency of administration by controlling drug release in the gastrointestinal tract, and target specificity to a particular site by placing drugs directly into the mucosal tract [2,3]. The literature signifies that different polymers, either natural or synthetic, have gained considerable interest in the pharmaceutical industry and academic research due to this mucoadhesive property that can deliver the oral dosage efficiently [4].…”