Pharmaceutical Research and Therapeutic Sciences

ABSTRACT

Biologic therapeutics, including proteins, peptides, monoclonal antibodies, hormones, enzymes, and nucleic acid-based medicines, have transformed the management of numerous chronic and life-threatening diseases. However, their clinical use remains largely dependent on parenteral administration because these macromolecules are highly susceptible to degradation in the gastrointestinal tract and exhibit poor intestinal permeability. Consequently, repeated injections are often required, leading to reduced patient compliance, needle-associated anxiety, increased healthcare costs, and diminished quality of life. These limitations have driven intensive research into alternative delivery strategies capable of enabling effective oral administration of biologics.

Nanoparticle-based drug delivery systems have emerged as one of the most promising approaches for overcoming the physiological and biochemical barriers that limit oral bioavailability. Advanced nanocarriers—including lipid nanoparticles, polymeric nanoparticles, liposomes, solid lipid nanoparticles, dendrimers, nanostructured lipid carriers, and biomimetic vesicles—can protect biologic molecules from acidic and enzymatic degradation, enhance mucus penetration, facilitate epithelial transport, and provide controlled or targeted drug release. Recent advances in materials science, surface engineering, and formulation technologies have significantly improved the stability, absorption, and therapeutic performance of orally administered biologics .

This narrative review critically examines current progress in nanoparticle-enabled oral delivery of injectable biologic therapeutics. We discuss the major gastrointestinal barriers to oral absorption, compare the characteristics of different nanoparticle platforms, and summarize recent preclinical and emerging clinical evidence supporting the oral conversion of biologics, including insulin, glucagon-like peptide-1 receptor agonists, monoclonal antibodies, and growth hormone, erythropoietin, interferons, and enzyme replacement therapies. The review also highlights key translational challenges related to formulation stability, manufacturing scalability, long-term safety, regulatory approval, and commercial development. Finally, emerging innovations, including biomimetic nanocarriers, stimuli-responsive nanoparticles, artificial intelligence-assisted formulation design, and precision nanomedicine, are discussed as promising strategies for accelerating clinical translation. Continued advances in nanoparticle engineering have the potential to transform injectable biologics into safe, effective, and patient-friendly oral medicines, redefining the future of biologic drug delivery.

Keywords: Oral Biologics; Injectable Therapeutics; Nanoparticle Drug Delivery; Oral Peptide Delivery; Monoclonal Antibodies; Protein Therapeutics; Intestinal Permeability; Bioavailability