Sustained Release Systems for Delivery of Therapeutic Peptide/Protein

Abstract

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, etc. 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 sustainedrelease 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.

Disclosing the Potential of Fluorinated Ionic Liquids as Interferon-Alpha 2b Delivery Systems

“…To overcome these complications, the development of efficient strategies to extend the half-life of therapeutic proteins through the administration routes has been in the research spotlight [ 10 ]. From those strategies, significant advances have been attained using drug delivery systems (DDSs) that aid the control of stability and release of the therapeutic proteins, protecting and maintaining their activity, improving their bioavailability, and guaranteeing their safety [ 10 , 11 , 12 , 13 , 14 ]. Amongst the different types of DDSs that have been developed, nanocarriers have found a place as promising tools to circumvent those challenges.…”

“…Amongst the different types of DDSs that have been developed, nanocarriers have found a place as promising tools to circumvent those challenges. They have been demonstrated to be non-invasive, safe, and targeted delivery methods [ 12 , 13 , 14 , 15 ]. However, there are still concerns from a biological and technological point of view that limit the usage of these systems, such as low stability, uncontrolled release of proteins, low encapsulation efficiency, expensive costs associated with the formulation and production of these systems, and difficulties in the scaling up of the process [ 12 , 13 , 14 , 15 ].…”

“…They have been demonstrated to be non-invasive, safe, and targeted delivery methods [ 12 , 13 , 14 , 15 ]. However, there are still concerns from a biological and technological point of view that limit the usage of these systems, such as low stability, uncontrolled release of proteins, low encapsulation efficiency, expensive costs associated with the formulation and production of these systems, and difficulties in the scaling up of the process [ 12 , 13 , 14 , 15 ]. Thus, even though some DDSs are already available in the market [ 15 ], there are still no fully effective and profitable nanocarriers.…”

Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer

“…Pluronic with polypropylene oxide as the central hydrophobic part and polyethylene oxide (PEO) as the hydrophilic part is a kind of nonionic thermosensitive triblock copolymer that may self-assemble into hydrogels under physiological temperature (37°C). However, its weak mechanical properties and fast clearance rate resulting from rapid degradation under physiological conditions always lead to uncontrollable release kinetics ( Nie et al, 2021 ). Therefore, in this work, chitosan was grafted onto the Pluronic backbone through the EDC/NHS reaction as previously reported.…”

Poly(disulfide)s: From Synthesis to Drug Delivery

“…With deepening of the research, the influence of poly(disulfide)s on the spatial structure and bioactivity of protein therapeutics also needs to be considered. 178 Therefore, the future design and development of poly-(disulfide)s need to consider the following aspects: steric hindrance and density of disulfide bonds in the polymer, the incorporation ratio of other synergistic functional groups, and more stimuli to promote the spatiotemporally controlled release of drugs. Overall, with their tunable chemical properties and variable stimuli responsiveness, poly(disulfide)s still hold great potency for on-demand drug delivery in the treatment of various diseases.…”