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用于2型糖尿病管理的利拉鲁肽给药系统的现状

Current status of Liraglutide delivery systems for the management of type 2 diabetes mellitus.

作者信息

Chatterjee Riti, Galave Vishal Sangita Babasaheb, Jindal Anil B

机构信息

Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333031, India.

出版信息

Drug Deliv Transl Res. 2025 Sep 6. doi: 10.1007/s13346-025-01965-y.

Abstract

Diabetes is a metabolic disorder of increasing global concern. Characterized by constantly elevated levels of glucose, severe β-cell dysfunction, and insulin resistance, it is the cause of a major burden on patients if not managed with therapeutic and lifestyle changes. The human body is slowly developing tolerance to many marketed antidiabetic drugs and the quest for the discovery of newer molecules continues. Liraglutide is a prominent GLP-1 receptor agonist which is administered daily via subcutaneous injection. In addition to lowering HbA1c levels, it is also known for promoting weight loss and improving cardiovascular outcomes. A variety of novel formulation strategies have been explored to improve its bioavailability and patient compliance. To address these limitations, various advanced drug delivery systems have been investigated, including polymeric nanoparticles, lipid-based nanocarriers, biodegradable microparticles, hydrogels, and dissolvable microneedles. These systems aim to prolong drug release, enhance mucosal penetration, increase stability, and reduce dosing frequency. While many of these platforms show promise in preclinical and early clinical studies, critical translational barriers remain. These include challenges in large-scale manufacturing, ensuring formulation sterility, achieving regulatory approval, and maintaining stability during storage and distribution.This review provides a comprehensive overview of the formulation strategies developed for liraglutide delivery, critically examines their pharmacokinetic and pharmacodynamic profiles, and evaluates the current state of clinical translation. By identifying both the potential and the limitations of these delivery technologies, the article aims to inform future research directions in GLP-1-based therapeutics and improve treatment outcomes for patients with T2DM.

摘要

糖尿病是一种日益引起全球关注的代谢紊乱疾病。其特征为血糖水平持续升高、严重的β细胞功能障碍和胰岛素抵抗,如果不通过治疗和生活方式改变进行管理,它将给患者带来重大负担。人体对许多市售抗糖尿病药物的耐受性正在逐渐增强,因此对新型分子的探索仍在继续。利拉鲁肽是一种著名的胰高血糖素样肽-1(GLP-1)受体激动剂,需每日皮下注射给药。除了降低糖化血红蛋白(HbA1c)水平外,它还以促进体重减轻和改善心血管结局而闻名。人们探索了各种新型制剂策略以提高其生物利用度和患者依从性。为解决这些局限性,人们研究了各种先进的药物递送系统,包括聚合物纳米颗粒、脂质基纳米载体、可生物降解的微粒、水凝胶和可溶解微针。这些系统旨在延长药物释放、增强黏膜渗透、提高稳定性并减少给药频率。虽然这些平台中的许多在临床前和早期临床研究中显示出前景,但关键的转化障碍仍然存在。这些障碍包括大规模生产方面的挑战、确保制剂无菌、获得监管批准以及在储存和分发过程中保持稳定性。本综述全面概述了为利拉鲁肽递送而开发的制剂策略,批判性地研究了它们的药代动力学和药效学特征,并评估了临床转化的现状。通过识别这些递送技术的潜力和局限性,本文旨在为基于GLP-1的治疗方法的未来研究方向提供信息,并改善2型糖尿病患者的治疗效果。

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