ADVANCED DELIVERY SYSTEMS FOR GENES, PEPTIDES, PROTEINS, AND VACCINE

The clinical translation of gene, peptide, protein, and vaccine therapeutics is fundamentally constrained by multiple biological barriers that limit their stability, bioavailability, and intracellular delivery. Despite their high specificity and therapeutic potential, biological macromolecules are susceptible to enzymatic degradation, immune clearance, poor membrane permeability, and intracellular sequestration. This chapter critically reviews advanced delivery technologies designed to address these challenges, with particular emphasis on engineered carrier systems. Key physiological and cellular barriers encountered during systemic circulation and cellular internalization, including serum instability, macrophage-mediated clearance, endosomal entrapment, and lysosomal degradation, are systematically examined. Non-viral gene delivery platforms based on lipid and polymer carriers are discussed, highlighting their roles in nucleic acid condensation, protection, endosomal escape, and intracellular trafficking. Strategies for peptide and protein delivery, including polymer conjugation and nanoparticle encapsulation, are reviewed with a focus on maintaining structural integrity and biological activity. Vaccine delivery approaches are evaluated in the context of nanoparticle-enabled antigen presentation and adjuvant co-delivery to enhance humoral and cellular immune responses. Emerging hybrid and stimuli-responsive delivery systems are also discussed, along with key translational and regulatory considerations that influence clinical applicability. Collectively, these advances underscore the critical importance of rationally designed delivery systems in enabling the therapeutic potential of macromolecular drugs.