Novel Drug Delivery Approaches for Biopharmaceuticals: Advances in mRNA, Protein, Peptide and Gene Delivery Systems

Abstract

Biopharmaceuticals, including messenger RNA (mRNA), therapeutic proteins, peptides and gene-based medicines, constitute a rapidly expanding class of advanced therapeutics with considerable potential for treating complex and previously difficult-to-manage diseases. However, their clinical application is frequently limited by enzymatic degradation, inadequate membrane permeability, short systemic half-life, immunogenicity and substantial intracellular delivery barriers. Particular emphasis is placed on lipid nanoparticles (LNPs), polymeric nanoparticles, liposomes, dendrimers, hydrogels, viral and non-viral vectors, and emerging biomimetic and exosome-based delivery systems. The review further considers advances in oral peptide delivery through permeation enhancers, targeted delivery approaches, stimuli-responsive carriers and strategies for improving cellular uptake and intracellular release. LNP technology is highlighted for its pivotal role in enabling the clinical translation of mRNA therapeutics and vaccines. In addition, the emerging application of artificial intelligence and computational approaches in carrier optimisation and formulation design is discussed. Comparative evaluation of these platforms considers delivery efficiency, stability, safety, scalability, therapeutic performance and translational potential. Six comparative tables and four schematic figures summarise key mechanisms, advantages, limitations and developmental status. Finally, major challenges involving toxicity, immunogenicity, regulatory requirements, manufacturing complexity and long-term stability are examined, alongside future opportunities for developing safer, more precise and clinically scalable biopharmaceutical delivery systems.