The long-term delivery of proteins and peptides using micro/nanoparticles: overview and perspectives

摘要

Recombinant insulin, the first commercialized therapeutic protein, was approved by the US FDA in 1982. Today, more than 900 bioactive proteins and peptides are going through different phases of clinical trials, including 330 monoclonal antibodies, 93 recombinant proteins and 250 vaccines for different indications, such as cancer, infection and autoimmune diseases [1]. Recently, the monoclonal antibodies nivolumab and pembrolizumab targeting the programmed death-1 receptor, are considered as the most exciting advances in targeted chemotherapy in various cancer types [2]. Concurrently, there is also the need for innovative delivery systems for biologic therapeutics (mostly proteins and peptides), valued at about US$ 480 billion in 2024 [3-5]. Therapeutic peptides and proteins possess several advantages compared with conventional small-molecule drugs; these include higher specificity, greater activity and less toxicity. Most of the therapeutic peptides and proteins are administered parenterally and, more specifically, via intravenous route. However, effective delivery of these agents to disease sites poses several challenges due to several factors, such as enzymatic degradation, short circulation half-lives and poor membrane permeability. Proteins also suffer from a physical, chemical and biological instability due to their complicated structures.