Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides

For buccal administration of proteins and peptides with therapeutic interest, formulations must be mucoadhesive and present one or more permeability enhancers as nanoparticles to cross the mucus layer (A) and permeate the epithelia (B) to finally reach the blood stream (C). A portion of carried proteins/peptides will be swallowed. Nanoparticles will protect the integrity of carried proteins and peptides while in contact with acidic pH and proteases secreted in the stomach (D), allowing the carried molecules to permeate the intestinal epithelia (E) to reach the bloodstream. [Display omitted] •Oral delivery of proteins and peptides with therapeutic interest can be achieved.•Buccal delivery of therapeutic proteins and peptides represents an attractive, unexplored type of delivery rout.•Nanoparticles represent useful tools to highly increase the effectiveness of proteins and peptides administered per os.•Size, zeta potential, mucoadhesion or physicochemical composition must be tailored according to carried protein/peptide.•Nanoparticle functionalization and/or inclusion of nanocarriers within mucoadhesive delivery systems can induce an overall increase of bioavailability of carried proteins and peptides. Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addre