MedinCell S.A, Jacou, France.
Expert Opin Drug Deliv. 2022 Aug;19(8):927-944. doi: 10.1080/17425247.2022.2105318. Epub 2022 Jul 28.
The development of long-acting injectables (LAIs) for protein and peptide therapeutics has been a key challenge over the last 20 years. If these molecules offer advantages due to their high specificity and selectivity, their controlled release may confer several additional benefits in terms of extended half-life, local delivery, and patient compliance.
This manuscript aims to give an overview of peptide and protein-based LAIs from an industrial perspective, describing both approved and promising technologies (with exceptions of protein engineering strategies and devices), their advantages and potential improvements to aid their access to the market.
Many LAIs have been developed for peptides, with formulations on the market for several decades. On the contrary, LAIs for proteins are still far from the market and issues related to manufacturing and sterilization of these products still need to be overcome. forming depots (ISFDs), whose simple manufacturing conditions and easy administration procedures (without reconstitution) are strong advantages, appear as one of the most promising technologies for the delivery of these molecules. In this regard, the approval of ELIGARD® in the early 2000's (which still requires a complex reconstitution process), paved the way for the development of second-generation, ready-to-use ISFD technologies like BEPO® and FluidCrystal®.
在过去的 20 年中，长效注射剂（LAIs）的开发一直是蛋白质和肽类治疗药物的关键挑战。如果这些分子因其高特异性和选择性而具有优势，那么它们的控制释放可能会在延长半衰期、局部递送和患者依从性方面带来额外的好处。
本文旨在从工业角度概述基于肽和蛋白质的 LAI，描述已批准和有前途的技术（不包括蛋白质工程策略和设备），及其优势和潜在改进，以帮助它们进入市场。
已经开发了许多用于肽的 LAI，其制剂已经上市几十年了。相比之下，用于蛋白质的 LAI 仍然远离市场，并且这些产品的制造和灭菌相关问题仍有待克服。原位形成储库（ISFDs）是一种很有前途的技术，其简单的制造条件和易于管理的程序（无需复溶）是其主要优势，似乎是这些分子递送的最有前途的技术之一。在这方面，ELIGARD®在 21 世纪初的批准（仍需要复杂的复溶过程）为第二代即用型 ISFD 技术（如 BEPO®和 FluidCrystal®）的开发铺平了道路。
