Enhanced Oral Bioavailability of Epalrestat SBE7-β-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation

Abstract

Background Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined. Purpose Current research aimed to fabricate inclusion complexation of EPL with SBE 7 β-CD (IC) and EPL/SBE 7 β-CD CS NPs (NP). Methods EPL was complexed with SBE 7 β-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug’s antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP. Results The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE 7 β-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be −6.6 kcal/mol. The calculated C max values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 μg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC 0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 μg/mL*h, respectively. Conclusion Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

Development, Characterization, in vitro Antidiabetic Activity of Chitosan−tripolyphosphate Nanoparticles Encapsulating Gmelina arborea Roxb. and Spondias pinnata (L.f) Kurz Aqueous Extracts

“…Particle size is the most important parameter in fabricating encapsulation of G. arborea and S. pinnata aqueous extracts. Nanoparticles can cross cellular membranes when the particle diameter is small and ultimately leads to efficient dispersion of the drug [23] . The larger particle size of SAE−CS−TPP (417±86 nm) compared to CS−TPP (105±1 nm) and of GAE−CS−TPP (113±5 nm) could reflect its higher EE (68.21±0.66 %) and LC (0.79±0.17 %).…”

“…Nanoparticles can cross cellular membranes when the particle diameter is small and ultimately leads to efficient dispersion of the drug. [23] The larger particle size of SAEÀ CSÀ TPP (417 � 86 nm) compared to CSÀ TPP (105 � 1 nm) and of GAEÀ CSÀ TPP (113 � 5 nm) could reflect its higher EE (68.21 � 0.66 %) and LC (0.79 � 0.17 %). Similar results were observed in void nanoparticles and hydrometha l extract derived from Punica granatum L. (Family: Punicaceae or Lythraceae) fruit peel encapsulated chitosan nanoparticles.…”

Comparison of Widely Targeted Metabolomics and Untargeted Metabolomics of Wild Ophiocordyceps sinensis

“…In previous studies, some important differential metabolites showed significant biological activity. Epalrestat is used to treat diabetes, kidney disease, heart disease, and retinopathy and can relieve diabetic neuropathic pain [ 33 , 34 ]. Flavin adenine dinucleotide (FAD) is an essential component of the body’s intracellular multifunctional oxidase system, involved in intracellular redox and electron transport systems in mitochondria, and associated with in vivo metabolism of sugars, fats, proteins, etc.…”

Bioequivalence Study of Epalrestat for Healthy Chinese Subjects

“…12 Epalrestat demonstrates limited solubility and dissolution rate, placing it in Class II of the Biopharmaceutics Categorization System categorization. 13 Hence, it is imperative to examine the diversity in absorption across various segments of the gastrointestinal tract, specifically focusing on the absence or minimal absorption occurring in the jejunum, since this may give rise to the double peak phenomenon. 14 In addition, it is worth noting that despite the use of epalrestat for managing diabetic complications, there exists a limited number of published pharmacokinetic research on this subject.…”

“…14 In addition, it is worth noting that despite the use of epalrestat for managing diabetic complications, there exists a limited number of published pharmacokinetic research on this subject. 9,13,15 The objective of this study was to assess the bioequivalence between a novel test formulation and a reference formulation of oral epalrestat (50 mg) in a population of healthy Chinese subjects.…”