Diabetes Research: Open Access
Article Type: Commentary
DOI: 10.36502/2024/droa.6186
Diab Res Open Access. 2024 May 18;5(1):05-08
Latest Pharmaceutical Development of Imeglimin Electrospinning Nanofibers for Diabetic Treatment
Hiroshi Bando1,2,3iD*, Hiroko Ogawa3, Masahiro Bando1
1Shikoku Division of Integrative Medicine Japan (IMJ), Tokushima, Japan
2Medical Research/Tokushima University, Tokushima, Japan
3Shuseikai Medical Corporation, Yoshinogawa Hospital, Tokushima, Japan
Corresponding Author: Hiroshi Bando ORCID iD
Address: Tokushima University /Medical Research, Nakashowa 1-61, Tokushima 770-0943, Japan.
Received date: 04 April 2024; Accepted date: 11 May 2024; Published date: 18 May 2024
Citation: Bando H, Ogawa H, Bando M. Latest Pharmaceutical Development of Imeglimin Electrospinning Nanofibers for Diabetic Treatment. Diab Res Open Access. 2024 May 18;5(1):05-08.
Copyright © 2024 Bando H, Ogawa H, Bando M. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.
Keywords: Gastrointestinal Adverse Effect, Imeglimin Electrospinning Nanofibers, Drug Delivery System, Solid Nanofibers Disintegration, Imeglimin, Twymeeg
Abbreviations: GIAE: Gastrointestinal Adverse Effect; DDS: Drug Delivery System
Abstract
Among oral hypoglycemic agents (OHAs), imeglimin (Twymeeg) has been evaluated in clinical practice with Trials of Imeglimin for Efficacy and Safety (TIMES) 1-3 international studies. However, its gastrointestinal adverse effect (GIAE) would be an actual problem. Recently, imeglimin electrospinning nanofibers have been reported as a potential buccal antidiabetic therapeutic approach, which shows absorption not via the gastrointestinal (GI) tract. Imeglimin nanofibers have a diameter of 361 ± 54 nm and a drug-loading (DL) of 23.5 ± 0.2 μg/mg of fibers. The solid nanofibers disintegration takes only 2 ± 1 seconds. This novel medicine is expected to lead to optimal therapeutic outcomes with better patient compliance.
Commentary
Across the world, the prevalence of type 2 diabetes (T2D) has increased [1]. Various anti-diabetic agents and oral hypoglycemic agents (OHAs) have then been introduced in clinical practice [2]. Among them, a novel tetrahydrotriazene derivative, imeglimin (Twymeeg), was approved for OHA. It has the dual function of increasing insulin secretion and decreasing insulin resistance via the mitochondrial pathway [3]. It has presented several effects through large research studies of the TIMES investigation [4]. TIMES stands for the Trials of Imeglimin for Efficacy and Safety international studies, which consist of 3 separate studies, TIMES 1–3. For TIMES, a total of 1100 patients were analyzed, providing 1000 mg of imeglimin twice a day [5]. The actual treatment of T2D by imeglimin has demonstrated satisfactory efficacy and safety outcomes.
However, certain drawbacks have been reported regarding gastrointestinal adverse effects (GIAE). They include nausea, constipation, vomiting, and diarrhea [6]. Furthermore, certain clinical problems have existed such as reduced absorption status by increased doses, probably from saturation of GI discomfort and the active transport mechanism [6]. These problems may bring poor compliance with medication, polypharmacy, and related instability of clinical progress in elderly patients [7].
As a recent beneficial topic for T2D patients, imeglimin electrospun nanofibers can be provided as a potential buccal antidiabetic therapeutic approach, which is not via the GI tract [8]. This is due to the fabricated nonfibers with imeglimin, characterized by its small diameter, drug-loading (DL) on the fiber, disintegration, and very rapid release of the medicine. The obtained data showed that imeglimin nanofibers have a diameter of 361 ± 54 nm and a DL of 23.5 ± 0.2 μg/mg of fibers. For X-ray diffraction (XRD), the solid nanofibers’ disintegration was proved to be only 2 ± 1 seconds, which means a surprisingly rapid disintegration ability. With this dosage, it can be suitable for buccal drug delivery, associated with complete release for 30 minutes. From the mentioned above, the imeglimin nanofibers will present the potential for providing via the buccal route, leading to optimal therapeutic outcomes with better patient compliance.
Regarding the buccal delivery route, some advantages are found, such as fast absorption, easy administration, low GI absorption, and bypassing first-pass metabolism influence [9]. For decades, several types of different fast-dissolving mucoadhesive formulations have been introduced from a pharmaceutical point of view. They include tablets, ointments, gels, transdermal patches, and also thin oral and buccal patches associated with the administration and fast absorption rate [9]. However, such thin oral film has certain limitations, which would be film thickness, dose uniformity. It may alter the mechanical properties and release rate of the agent [10]. Smart buccal delivery can utilize advanced materials to obtain optimal absorption and delivery of medical agents to their ultimate target [11]. From the mentioned above, current electrospun nanofibers would be the key smart buccal drug delivery system (DDS) associated with beneficial advantages. They include own mechanical properties and ultra-rapid speed of disintegration and release rates of the drug at less than 2 seconds [12]. The electrospinning method has been known to produce nanofibers by the use of high voltage. They make a capillary tube of polymer solution to forming nanofibers [13]. Electrospun nanofibers can include various applications, such as DDS, tissue engineering, and wound dressing [13]. They also have higher porosity and a predominant surface-to-volume ratio, leading to carrying a large amount of loading drug, fast releasing, and absorption of the medicine [12,14].
From a DDS point of view, oral fast-dissolving types have been recently in focus [15]. They have some categories such as lyophilized systems, compressed table-based systems, and oral fast-dissolving films, which have various patents. These types are beneficial for pediatric, geriatric, and traveling patients who cannot have readily accessible water [16]. Various parameters are present for evaluating such films, where fast-dissolving films seem to be predominant for delivering drugs and gaining fasting therapeutic blood concentration levels, which are compared to other oral previous dosage forms [15].
In the latest report, dual-loaded nanofibers have been applied to another medical agent, sildenafil, used for erectile dysfunction (ED) [17]. By a pharmaceutical approach, the detailed bioavailability was evaluated for disintegration, measuring diameter, drug-loading effect, and drug release profile. In this case, sildenafil and the root extract of glycyrrhizin (Glycyrrhiza glabra) were mixed as a natural sweetener for absorption from the buccal cavity. The release of two elements showed a burst release in 1 min, followed by a gradual increase until 120 min of complete release. Further exams of in vitro cell viability were conducted for the application of two drugs on human skin fibroblast cells. Then, the combined ratio of 1:4 of sildenafil/glycyrrhizin demonstrated >80% of cell viability after 24-hour cell exposure. Consequently, these dual-loaded nanofibers can present the potential buccal therapeutic approach route for erectile dysfunction treatment.
The clinical use of mucoadhesive polymers for medication in buccal drug delivery has attracted attention. The buccal mucosa seems to be a convenient and useful accessible region for drug administration for systemic and local delivery [18]. Mucoadhesion includes functional chemical interactions of mucin and polymers. There is a variety of mucoadhesive forms, such as tablets, disks, patches, gels, and ointments. Among them, buccal patches can offer comfort and greater flexibility than others. Smart materials have been developed, including liposome-based patches, stimuli-responsive hydrogels, polymeric micelles, and so on. With this effective carrier capacity, patients can obtain improved drug bioavailability, prolonged residence time of the agent at the absorption site, and improved patient compliance. Some types of different methods are present, including electrospraying, electrospinning, and three-dimensional printing techniques. These are evaluated to be novel and effective measures for the preparation of buccal patches associated with beneficial unique characteristics.
In summary, recently developed imeglimin nanofibers seem to show future potential with expectation. They can be administered via the oral and buccal route, which may achieve optimal therapeutic results with improving patient compliance. It is expected that this report will contribute to diabetic practice and research in the future.
Conflict of Interest
The author has read and approved the final version of the manuscript. The author has no conflicts of interest to declare.
Funding
There was no funding received for this paper.
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