Recent Developments in Protein and Peptide Parenteral Delivery Approaches

Abstract

Discovery of insulin in the early 1900s initiated the research and development to improve the means of therapeutic protein delivery in patients. In the past decade, great emphasis has been placed on bringing protein and peptide therapeutics to market. Despite tremendous efforts, parenteral delivery still remains the major mode of administration for protein and peptide therapeutics. Other routes such as oral, nasal, pulmonary and buccal are considered more opportunistic rather than routine application. Improving biological half-life, stability and therapeutic efficacy is central to protein and peptide delivery. Several approaches have been tried in the past to improve protein and peptide in vitro/in vivo stability and performance. Approaches may be broadly categorized as chemical modification and colloidal delivery systems. In this review we have discussed various chemical approaches such as PEGylation, hyperglycosylation, mannosylation, and colloidal carriers including microparticles, nanoparticles, liposomes, carbon nanotubes and micelles for improving protein and peptide delivery. Recent developments on in situ thermosensitive gel-based protein and peptide delivery have also been described. This review summarizes recent developments on some currently existing approaches to improve stability, bioavailability and bioactivity of peptide and protein therapeutics following parenteral administration.

Intestinal permeation enhancers for oral peptide delivery

“…and low values (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) [165]. The hydrophobic moiety of the surfactant also influences enhancement action.…”

Novel Delivery Systems for Improving the Clinical Use of Peptides

“…Liposomes are vesicles, which have a bilayer phospholipid membrane allowing entrapping hydrophilic peptides inside the protective shell. As in the other delivery systems, liposomes protect the peptide from degradation, prolong circulation time, and increase bioavailability (Patel et al, 2014). Liposomes have been demonstrated to serve as a carrier for various peptides, such as insulin, vasoactive intestinal polypeptide, and calcitonin (Du and Stenzel, 2014); however, some major issues related to their stability need to be resolved (Patel et al, 2014).…”

“…Various polymer-based delivery systems have been applied for peptides using both synthetic and natural materials, including gelatin, hyaluronic acid, cellulose, chitosan, poly(lactic-coglycolic) acid (PLGA), polycaprolactones, polyanhydrides, and cyclodextrins (Jain et al, 2013;Du and Stenzel, 2014;Mitragotri et al, 2014;Patel et al, 2014). The fabrication of polymer-based peptide delivery systems can be performed by several techniques, such as phase separation, solvent evaporation, or spraying.…”

Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer

“…This challenge can be addressed through both molecular design to prolong half life (e.g., PEGylation, acetylation, fusion to albumin, or the Fc region of an antibody) as well as formulation (sustained release dosage forms). This is well beyond the scope of this article, and the reader is encouraged to consult recent articles on the topics, for example (8). …”