Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Drug Dev Res. 2021 Nov;82(7):927-944. doi: 10.1002/ddr.21832. Epub 2021 May 14.
Advancement in biotechnology provided a notable expansion of peptide and protein therapeutics, used as antigens, vaccines, hormones. It has a prodigious potential to treat a broad spectrum of diseases such as cancer, metabolic disorders, bone disorders, and so forth. Protein and peptide therapeutics are administered parenterally due to their poor bioavailability and stability, restricting their use. Hence, research focuses on the oral delivery of peptides and proteins for the ease of self-administration. In the present review, we first address the main obstacles in the oral delivery system in addition to approaches used to enhance the stability and bioavailability of peptide/protein. We describe the physiochemical parameters of the peptides and proteins influencing bioavailability in the systemic circulation. It encounters, many barriers affecting its stability, such as poor cellular membrane permeability at the GIT site, enzymatic degradation (various proteases), and first-pass hepatic metabolism. Then describe the current approaches to overcome the challenges mentioned above by the use of absorption enhancers or carriers, structural modification, formulation and advance technology.
生物技术的进步显著拓展了肽类和蛋白质治疗药物的应用领域,包括抗原、疫苗和激素等。它们具有治疗广泛疾病的巨大潜力,如癌症、代谢紊乱、骨骼疾病等。由于肽类和蛋白质的生物利用度和稳定性较差,需要通过注射给药,这限制了它们的应用。因此,研究重点集中在肽类和蛋白质的口服递送,以实现方便的自我给药。在本综述中,我们首先讨论了口服递送系统中存在的主要障碍,以及用于提高肽/蛋白质稳定性和生物利用度的方法。我们描述了影响全身循环中生物利用度的肽类和蛋白质的物理化学参数。它在胃肠道部位会遇到许多影响其稳定性的障碍,如细胞膜通透性差、酶降解(各种蛋白酶)和首过肝脏代谢。然后描述了目前使用吸收增强剂或载体、结构修饰、制剂和先进技术来克服上述挑战的方法。