Challenges and Strategies to Enhance the Systemic Absorption of Inhaled Peptides and Proteins

Abstract

Proteins and peptides-based therapeutics are making substantial access to the market due to their obvious advantages of strong potency, high specificity and desirable safety profile. However, most clinical products are mainly delivered via parenteral route with inferior convenience. Lung is an attractive non-invasive alternative passage for systemic administration of biologics with numerous outstanding features, as examples of large absorptive surface area, extensive vascularization and mild local microenvironment. Even so, mucociliary clearance, alveolar macrophage phagocytosis, enzymatic metabolism, pulmonary surfactant adsorption and limited epithelium permeability constitute major obstacles affecting the systemic absorption of inhaled proteins and peptides. This article begins by giving a brief overview of challenges for the systemic absorption of inhaled proteins and peptides, and then goes on to a comprehensive review of possible strategies for enhanced pulmonary absorption, including chemical modification, addition of protease inhibitors, incorporation of absorption enhancers, modification with fusion proteins and development of particulate-based drug delivery systems. These strategies can provide enhanced transmembrane absorption capacity while avoiding pulmonary clearance, offering a valuable reference for designing pulmonary delivery systems of protein and peptide drugs.

Identification of DPP‐IV inhibitory peptides derived from buffalo colostrum: Mining through bioinformatics, in silico and in vitro approaches

“…Considering ADMET analysis, further studies focusing on the improvement of hydrophobicity/hydrophilicity with respect to Log P and D values, which can improve the peptides' ability to be absorbed (HIA and MDCK), may be needed to develop these peptides as therapeutics. These can be chemical modification, using absorption enhancers, protease inhibitors along with the peptides, and conjugating with fusion proteins and drug delivery systems 31 …”

“…These can be chemical modification, using absorption enhancers, protease inhibitors along with the peptides, and conjugating with fusion proteins and drug delivery systems. 31 Prior studies have utilized molecular docking studies to elucidate the interactions of potential inhibitors of DPP-IV. The characteristic feature of DPP-IV is the presence of the catalytic triad in the order of Ser-Asp-His, comprising of a conserved motif GWSYGG around the catalytic residue Ser in the form of α/β-hydrolase domain and a pair of Glu residues in β-propeller domain, which is highly conserved and vital for the enzyme activity.…”

The role of peptides in reversing chemoresistance of breast cancer: current facts and future prospects

“…8 Peptides as a drug moiety: current challenges and possible solutions As an anticancer peptide with the effect of reversing the resistance of chemotherapeutic drugs and treating malignant tumors such as breast cancer, it has the characteristics of easy synthesis and modification, various modes of administration, and difficulty in producing multidrug resistance (Chen G. et al, 2022). Moreover, the peptide itself has strong targeting, small adverse reactions, and easy separation and transformation (Qin et al, 2022). Although many peptides have been found to have good anti-tumor activity, the development of peptide drugs faces many challenges.…”

Advances in Pulmonary Drug Delivery Systems and Inhalation Formulations

“…Inhaled biologics are a hot topic for both local and systemic efficacy. Mao et al [2] provide a comprehensive review that discusses challenges in the systemic absorption of inhaled proteins and peptides, and potential strategies for enhancing pulmonary absorption of inhaled biologics for systemic effects.…”