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治疗性肽长效递药制剂的最新进展。

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides.

机构信息

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutics Science, Monash University, Parkville Campus, Parkville, Victoria 3052, Australia.

Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, Victoria 3168, Australia.

出版信息

ACS Appl Bio Mater. 2023 Sep 18;6(9):3532-3554. doi: 10.1021/acsabm.3c00193. Epub 2023 Jun 9.

Abstract

Recent preclinical and clinical studies have focused on the active area of therapeutic peptides due to their high potency, selectivity, and specificity in treating a broad range of diseases. However, therapeutic peptides suffer from multiple disadvantages, such as limited oral bioavailability, short half-life, rapid clearance from the body, and susceptibility to physiological conditions (e.g., acidic pH and enzymolysis). Therefore, high peptide dosages and dose frequencies are required for effective patient treatment. Recent innovations in pharmaceutical formulations have substantially improved therapeutic peptide administration by providing the following advantages: long-acting delivery, precise dose administration, retention of biological activity, and improvement of patient compliance. This review discusses therapeutic peptides and challenges in their delivery and explores recent peptide delivery formulations, including micro/nanoparticles (based on lipids, polymers, porous silicon, silica, and stimuli-responsive materials), (stimuli-responsive) hydrogels, particle/hydrogel composites, and (natural or synthetic) scaffolds. This review further covers the applications of these formulations for prolonged delivery and sustained release of therapeutic peptides and their impact on peptide bioactivity, loading efficiency, and (/) release parameters.

摘要

最近的临床前和临床研究集中在治疗性肽这一活跃领域,因为它们在治疗广泛疾病方面具有高效能、高选择性和高特异性。然而,治疗性肽存在多种缺点,例如口服生物利用度有限、半衰期短、在体内清除速度快以及易受生理条件(如酸性 pH 值和酶解)影响。因此,为了有效治疗患者,需要高肽剂量和给药频率。最近的药物制剂创新通过提供以下优势,大大改善了治疗性肽的给药:长效递送、精确的剂量给药、保持生物活性和提高患者顺应性。本文综述了治疗性肽及其在递送上的挑战,并探讨了最近的肽递送制剂,包括微/纳米颗粒(基于脂质、聚合物、多孔硅、二氧化硅和刺激响应性材料)、(刺激响应性)水凝胶、颗粒/水凝胶复合材料和(天然或合成)支架。本文进一步综述了这些制剂在延长治疗性肽的递送和持续释放方面的应用,以及它们对肽生物活性、载药效率和(/)释放参数的影响。

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