Proteins and peptides play essential roles in almost all biochemical processes in the human body. As for example protein and peptide facilitates metabolism through enzymes as amylase, pepsin and trypsin, defending against pathogens with antibodies as, defensins, vancomycin and cathelicidins and controlling blood sugar levels via hormones like insulin. Similarly helps in generating cell signaling pathway for smooth regulation of organ functioning, promotes immune response as lysozymes, molecular transport and most important it regulates gene expressions. Additionally, peptides and proteins such as Serotonin, ATN-161, Insulin, Alpha-1 antitrypsin, and α₁-antitrypsin play a vital role in several clinical disorders, including cancer, diabetes, and hypertension (Deb et al., 2019; Kumar and Malviya, 2024). Proteins and peptides might be appealing therapeutic agents for the prevention of many ailments due to their diverse activities and participation in several diseases. Protein and peptide physicochemical characteristics and the gastrointestinal system's physiological milieu affect how effectively oral protein and peptide dispersion work. Because of their precise spatial structure, proteins are susceptible to hydrolysis and possible loss of action due to the gastrointestinal tract's pH and enzymes. Moreover, the stomach is acidic (Rhoads and Friedberg, 1997; Yap et al., 2000; Mruk et al., 2014). Therefore, the bioavailability of oral peptide or protein medications can be enhanced by improving the system architecture by addressing numerous critical components. These components include evading the GIT's biological and physical barriers, making it easier for macromolecules to enter the systemic circulation, and shielding peptides and proteins' fine spatial structures from degradation by GIT enzymes. Pharmacologically speaking, the creation of peptide and protein medications has mostly concentrated on novel drug delivery systems and molecular alterations (Grant et al., 2020; Bohush et al., 2016; O'Day, 2020; Hayashi, 2022). The method of administering medicine or other pharmacological chemicals to have a therapeutic effect is known as drug delivery (Robinson, 2014; Alzheimer's Association, 2020) medicine distribution has received much attention in the pharmaceutical industry in recent decades as a result of the recognition that the route of delivery of medicine might influence its efficacy. Choosing the best delivery system for a particular medication can maximize the drug's effectiveness within the body.

Drug delivery methods, which reduce off-target accumulation, facilitate therapeutic transport to the desired site, and facilitate patient adherence, have made several pharmaceutical treatments that improve patient health conceivable (Long et al., 2023; Gunes et al., 2022; Yang et al., 2023). As treatment modalities extended beyond minuscule molecules to encompass nucleic acids, peptides, proteins, and antibodies, drug delivery methods had to adapt to meet the new challenges (et al., 2022).

Proteins as well as peptides make useful building blocks for CNS therapies having strong effects on the brain followed by their effective delivery at targeted site. Their relationship to the BBB and less pharmacokinetics is major obstacles to such progress (Perez et al., 2015; Sahoo and Labhasetwar, 2003). Certain peptides go across the blood-brain barrier by trans-endothelial diffusion, whereas others use saturable transporters. Certain regulatory proteins can pass across the blood-brain barrier (BBB), whereas antibodies can enter the central nervous system via extracellular pathways. Glycoproteins and certain antibody fragments can be absorbed and passed past the blood-brain barrier via mechanisms known as adsorptive endocytosis/transcytosis. Many peptides and proteins exit the brain through saturation efflux processes, and enzymatic activity in the blood, brain, or blood-brain barrier acts as an effective barrier to other substances. Many drugs and health issues affect the inflow and transporters for efflux (Panda et al., 2014; Brack and Orgel, 1975; Potekhin et al., 2001). Therapeutic development has a great deal of promise when techniques are employed to control the communication between the BBB protein and peptides. Increasing small peptide trans endothelial diffusion is one of these strategies, along with inhibiting efflux transporters with antisense molecules, upregulating saturable influx transporters with allosteric regulators and other posttranslational techniques, and enhancing pharmaco-kinetic parameters to avoid tissue sequestration, short half-lives, and enzymatic degradation (Wagner et al., 2005; Moutevelis and Woolfson, 2009).