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

Abstract

Mucoadhesive nanoparticles represent a potential drug delivery strategy to enhance the therapeutic efficacy in oral therapy. This study assessed the prospective of developing HPMC- and PLGA-based nanoparticles using a nanospray drier as a mucoadhesive extended release drug delivery system for sitagliptin and evaluated their potential in an animal model. Nanoparticles were prepared using a Buchi® B-90 nanospray drier. Optimization of particle size was performed using response surface methodology by examining the influence of spray-drying process variables (inlet temperature, feed flow, and polymer concentration) on the particle size. The prepared nanoparticles were characterized for various physicochemical characteristics (yield, drug content, morphology, particle size, thermal, and crystallographic properties) and assessed for drug release, stability, and mucoadhesive efficacy by ex vivo and in vivo studies in rats. A linear model was suggested by the design of the experiments to be the best fit for the generated design and values. The yield was 77 ± 4%, and the drug content was 90.5 ± 3.5%. Prepared nanoparticles showed an average particle size of 448.8 nm, with a narrow particle size distribution, and were wrinkled. Thermal and crystallographic characteristics showed that the drug present in the nanoparticles is in amorphous dispersion. Nanoparticles exhibited a biphasic drug release with an initial rapid release (24.9 ± 2.7% at 30 min) and a prolonged release (98.9 ± 1.8% up to 12 h). The ex vivo mucoadhesive studies confirmed the adherence of nanoparticles in stomach mucosa for a long period. Histopathological assessment showed that the formulation is safe for oral drug delivery. Nanoparticles showed a significantly higher (p < 0.05) amount of sitagliptin retention in the GIT (gastrointestinal tract) as compared to control. The data observed in this study indicate that the prepared mucoadhesive nanoparticles can be an effective alternative delivery system for the oral therapy of sitagliptin.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

“…An accurately weighed quantity of optimized SLN (CL10) was sealed separately in light resistant glass vials at ambient temperature (25 ± 1 °C) and under refrigerated conditions (4 ± 0.5 °C) up to 3 months [ 38 ]. The stability of SLN was examined by assessing the drug content, particle size, and drug release during the storage period.…”

Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

“…This can be attributed to compound degradation due to pH variation and enzymatic activity in the gastrointestinal (GI) tract or poor permeability across intestinal biological membranes [ 119 , 121 , 122 ]. Delivery systems such as carbohydrate-functionalized polymeric nanoparticles are able to provide protection from degradation in the GI tract, increase absorption by the intestinal epithelium due to its mucoadhesive properties (e.g., PLGA, chitosan, and alginate) and cell or tissue-targeted delivery and sustained release [ 121 , 123 , 124 , 125 , 126 ]. Gentamicin (GM) is an antibiotic that can only be administered in parenteral form or in topical formulations, and it cannot be orally administered due to enzymatic degradation and poor bioavailability.…”

Enhancement of oral bioavailability of natural compounds and probiotics by mucoadhesive tailored biopolymer-based nanoparticles: A review

“…Ex vivo studies of mucoadhesion are carried out by evaluating the attachment of NPs to fresh stomach or intestinal mucosa. Additionally, the spectrophotometric or chromatographic quantification of the active compounds that have been released from the adhered NPs could also be an indirect evaluation method (Nair et al, 2019;Esposito et al, 2020;Liu et al, 2019).…”

“…Hydroxypropyl methylcellulose (HPMC) has also been used in combination with PLGA to produce NPs by nanospray-drying, as a mucoadhesive delivery system for sitagliptin, an antidiabetic compound with dipeptidylpeptidase-4 (DPP-4) enzyme inhibitory capacity (Nair et al, 2019). The NPs, with a particle size of ≈ nm and an irregular and wrinkled shape, showed high capacity to reside in the stomach mucosa for up to 4 h due to the mucoadhesive property of HPMC, and prolonged release in the rat GI tract due to the controlled release properties of PLGA.…”