Functionalized zein nanoparticles targeting neonatal Fc receptor to enhance lung absorption of peptides

Peptides have a distinguished therapeutic potential for several chronic conditions, and more than 80 peptides exist in the global market. However, most of these marketed peptide drugs are currently delivered intravenously or subcutaneously due to their fast degradation and limited absorption through non-invasive routes. The pulmonary route is favored as a non-invasive route. Neonatal Fc receptor (FcRn) is expressed in adult human lungs and has a role in enhancing the pulmonary absorption of monoclonal antibodies. In this work, we developed and characterized candidate protein delivery systems for the pulmonary administration of peptides. The prepared bare and loaded zein nanoparticles (ZNPs), targeted, physically, and covalently PEGylated ZNPs showed hydrodynamic diameters between 137 and 155 nm and a narrow distribution index. Insulin, which was used as a protein model, showed an association efficiency of 72%, while the FcRn-targeted peptide conjugation efficiency was approximately 68%. The physically adsorbed poloxamer 407 on insulin-loaded ZNPs showed slower and controlled insulin release. The in vitro cell culture model consists of the NCI-H441 epithelial cell line, which confirmed its expression of the targeted receptor, FcRn. The safety of ZNPs was verified after incubation with both cell lines of the in vitro pulmonary model, namely NCI-H441 and HPMEC-ST1.6R, for 24 h. It was observed that targeted ZNPs enhanced insulin permeability by showing a higher apparent permeation coefficient than non-targeted ZNPs. Overall, both targeted PEGylated ZNPs showed to be suitable peptide carriers and adequately fit the demands of delivery systems designed for pulmonary administration.

Automated summary

Peptides have great potential for treating chronic conditions and there are more than 80 peptides available in the global market. However, most of the marketed peptide drugs are administered intravenously or subcutaneously due to their fast degradation and limited absorption through non-invasive routes. In this study, candidate protein delivery systems for pulmonary administration of peptides were developed and characterized. The targeted PEGylated zein nanoparticles (ZNPs) showed promising results in enhancing insulin permeability and are suitable as peptide carriers for pulmonary delivery.