Development of Imeglimin Electrospun Nanofibers as a Potential Buccal Antidiabetic Therapeutic Approach

Abstract

The prevalence of type 2 diabetes (T2D) has been growing worldwide; hence, safe and effective antidiabetics are critically warranted. Recently, imeglimin, a novel tetrahydrotriazene compound, has been approved for use in T2D patients in Japan. It has shown promising glucose-lowering properties by improving pancreatic beta-cell function and peripheral insulin sensitivity. Nevertheless, it has several drawbacks, including suboptimal oral absorption and gastrointestinal (GI) discomfort. Therefore, this study aimed to fabricate a novel formulation of imeglimin loaded into electrospun nanofibers to be delivered through the buccal cavity to overcome the current GI-related adverse events and to provide a convenient route of administration. The fabricated nanofibers were characterized for diameter, drug-loading (DL), disintegration, and drug release profiles. The data demonstrated that the imeglimin nanofibers had a diameter of 361 ± 54 nm and DL of 23.5 ± 0.2 μg/mg of fibers. The X-ray diffraction (XRD) data confirmed the solid dispersion of imeglimin, favoring drug solubility, and release with improved bioavailability. The rate of drug-loaded nanofibers disintegration was recorded at 2 ± 1 s, indicating the rapid disintegration ability of this dosage form and its suitability for buccal delivery, with a complete drug release after 30 min. The findings of this study suggest that the developed imeglimin nanofibers have the potential to be given via the buccal route, thereby achieving optimal therapeutic outcomes and improving patient compliance.

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing

“…All fibrous systems were fabricated according to the modified methods of these previous studies Aburayan et al, 2020 , Alamer et al, 2023 , Alshaya et al, 2022 . A solution of PVP and ethanol (8 % w/v) was stirred for one hour at an ambient temperature on a magnetic stirrer.…”

“…A serial dilution of six ribavirin concentrations (200–6.25 μg/mL) was prepared by dissolving ribavirin in phosphate buffer saline (PBS, pH 6.8). An HPLC set-up of Waters e2695 was utilized that consists of a Waters 600 binary pump, Waters® 717 plus autosampler, and Waters 2489 UV/detector (Waters Technologies Corporation, Milford, MA, USA), which is similar to the HPLC set-up of the previous study of Alamer et al, (2023) . Ribavirin was identified according to a modified method of Inoue et al, 2004 , D'Avolio et al, 2006 , and Haggag et al, 2014 using a C 18 column (4.6 mm × 250 mm, 5 μm), while the mobile phase was 1 % v/v triethanolamine (pH 3.9).…”

“…The DL and EE% of the ribavirin-loaded PVP/CD fibers and ribavirin-loaded PVP-only fibers were quantified by dissolving three pieces of the fiber at a weight of 4 ± 0.2 mg in PBS (pH 6.8), for four hours at room temperature, according to a slightly modified method of Alamer et al, (2023) . The samples were measured after the complete dissolving of the ribavirin-loaded fibers and subjected to the previously HPLC-developed method.…”

“…The disintegration of blank PVP/CD fibers, PVP-only fibers, ribavirin-loaded PVP/CD fibers, and ribavirin-loaded PVP-only fibers was evaluated using the petri dish method, according to the previous studies of Alamer et al, 2023 , Alshaya et al, 2022 and Alkahtani et al, 2021 . Briefly, certain weights of each nanofibrous system were positioned inside Petri dishes half-filled with pre-warmed PBS (37 °C and pH 6.8), mimicking the pH of an open wound that ranges from 6.5 to 8.5 ( Louisa et al, 2017 ).…”

“…The drug release rate of ribavirin-loaded PVP/CD fibers and ribavirin-loaded PVP fibers were assessed after weighing a certain amount of both fibrous systems and dissolving them into 20 mL PBS (pH 6.8) using custom-made sinkers to keep the fibers at the bottom of the vials, by a modified method of the release studies of Alamer et al, 2023 , Alshaya et al, 2022 and Alkahtani et al, 2021 . The vials were kept inside a trembling incubator (Excella E24 Incubator Shaker Series, New Brunswick Scientific Co., Enfield, CT, USA) at a shaking rate of 100 RPM and a temperature of 37 degrees Celsius.…”