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Enhancing the Buccal Mucosal Delivery of Peptide and Protein Therapeutics

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Abstract

With continuing advances in biotechnology and genetic engineering, there has been a dramatic increase in the availability of new biomacromolecules, such as peptides and proteins that have the potential to ameliorate the symptoms of many poorly-treated diseases. Although most of these macromolecular therapeutics exhibit high potency, their large molecular mass, susceptibility to enzymatic degradation, immunogenicity and tendency to undergo aggregation, adsorption, and denaturation have limited their ability to be administered via the traditional oral route. As a result, alternative noninvasive routes have been investigated for the systemic delivery of these macromolecules, one of which is the buccal mucosa. The buccal mucosa offers a number of advantages over the oral route, making it attractive for the delivery of peptides and proteins. However, the buccal mucosa still exhibits some permeability-limiting properties, and therefore various methods have been explored to enhance the delivery of macromolecules via this route, including the use of chemical penetration enhancers, physical methods, particulate systems and mucoadhesive formulations. The incorporation of anti-aggregating agents in buccal formulations also appears to show promise in other mucosal delivery systems, but has not yet been considered for buccal mucosal drug delivery. This review provides an update on recent approaches that have shown promise in enhancing the buccal mucosal transport of macromolecules, with a major focus on proteins and peptides.

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ACKNOWLEDGMENTS AND DISCLOSURES

T. Caon and C.M.O. Simões thank, respectively, CAPES/MEC and CNPq/MCTI, for providing his PhD scholarship (BEX 12349/12-7/“Sandwich” PhD Program) and her research fellowship. The work is also supported in part by the Australian National Health and Medical Research Council (number #1042481). RSN acknowledges fellowship support by the National Health and Medical Research Council.

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Authors and Affiliations

  1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Thiago Caon, Liang Jin & Joseph A. Nicolazzo

  2. Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina Campus Universitário, Trindade, 88040-900, Florianópolis, SC, Brazil

    Thiago Caon & Cláudia M. O. Simões

  3. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Raymond S. Norton

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  1. Thiago Caon
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  3. Cláudia M. O. Simões
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Correspondence to Joseph A. Nicolazzo.

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Caon, T., Jin, L., Simões, C.M.O. et al. Enhancing the Buccal Mucosal Delivery of Peptide and Protein Therapeutics. Pharm Res 32, 1–21 (2015). https://doi.org/10.1007/s11095-014-1485-1

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