CHALLENGES WITH PEPTIDE AND PROTEIN THERAPEUTICS
Although protein and peptide therapeutics possess high impact in health care, delivery of these agents is limited due to numerous factors. Large molecular size and hydrophilic nature of peptides and proteins prevent these molecules from traversing biological membranes such as gastrointestinal mucosa [1,2]. Such physicochemical properties may cause poor absorption and bioavailability for orally administered protein or peptide drugs. Moreover, these molecules are digested by proteolytic enzymes that are expressed highly in gastrointestinal tract . First-pass metabolism by the liver following oral administration eliminates significant amounts of absorbed drugs [2,3]. Furthermore, low gastric acid pH in the stomach can cause chemical degradation ofprotein/peptide drugs . Therefore oral delivery is the least favorable route for protein or peptide drugs. Slight modifications of the native confirmation may result in aggregations leading to partial or complete loss of activity [2,4]. The short half-lives of peptide and protein drugs require repeated administration to maintain therapeutic levels [2,3,5]. Nonetheless, frequent intravitreal injections are not patient compliant and may precipitate other complications such as retinal hemorrhage and detachment as is the case with bevacizumab [3,5]. Alternative routes such as nasal and pulmonary routes have been considered for peptide and protein delivery. Despite large surface area and highly vascularized tissue, pulmonary administration has shown limited bioavailability of protein drugs due to degradation by macrophage enzymes and rapid clearance by nasal and respiratory tracts .