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治疗性肽/蛋白递释的持续释放系统。

Sustained Release Systems for Delivery of Therapeutic Peptide/Protein.

机构信息

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100, China.

出版信息

Biomacromolecules. 2021 Jun 14;22(6):2299-2324. doi: 10.1021/acs.biomac.1c00160. Epub 2021 May 6.

Abstract

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, . owing to their high biocompatibility, specificity, and therapeutic efficacy. However, due to their immunogenicity, instability stemming from its complex tertiary and quaternary structure, vulnerability to enzyme degradation, and rapid renal clearance, the clinical application of protein/peptide therapeutics is significantly confined. Though nanotechnology has been demonstrated to prevent enzyme degradation of the protein therapeutics and thus enhance the half-life, issues such as initial burst release and uncontrollable release kinetics are still unsolved. Moreover, the traditional administration method results in poor patient compliance, limiting the clinical application of protein/peptide therapeutics. Exploiting the sustained-release formulations for more controllable delivery of protein/peptide therapeutics to decrease the frequency of injection and enhance patient compliance is thus greatly meaningful. In this review, we comprehensively summarize the substantial advancements of protein/peptide sustained-release systems in the past decades. In addition, the advantages and disadvantages of all these sustained-release systems in clinical application together with their future challenges are also discussed in this review.

摘要

肽/蛋白治疗药物在癌症、糖尿病等多种疾病的临床治疗中得到了广泛应用。由于其具有高生物相容性、特异性和治疗效果。然而,由于其免疫原性、复杂的三级和四级结构导致的不稳定性、易被酶降解以及快速肾清除率,蛋白/肽治疗药物的临床应用受到了显著限制。尽管纳米技术已被证明可以防止蛋白治疗药物的酶降解,从而延长半衰期,但仍存在初始突释释放和不可控释放动力学等问题尚未解决。此外,传统的给药方式导致患者顺应性差,限制了蛋白/肽治疗药物的临床应用。因此,开发用于更可控地递送蛋白/肽治疗药物的缓释制剂,以减少注射频率并提高患者顺应性具有重要意义。在这篇综述中,我们全面总结了过去几十年中蛋白/肽缓释系统的重要进展。此外,我们还讨论了所有这些缓释系统在临床应用中的优缺点及其未来的挑战。

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