Abstract

Macromolecules, specifically peptides, proteins, nucleic acids (for instance mRNA, siRNA, miRNA), etc. have been anticipated to be exclusive theranostic agents and potentially being applied for the diagnosis and treatment of various dreadful and intractable ailments. Although, macromolecule therapeutics are overpriced, they may alleviate countless downsides of small molecule drugs, as they are certainly tissue-selective, biocompatible, and economically scaled-up. However, unfavorable characteristics viz, rapid degradation in plasma, rapid metabolism, negative-charge density and conventional administration techniques leading to poor patient compliance, restrict the clinical uses of peptide/protein/nucleic acid therapeutics. The fate of macromolecule-based therapeutics depends upon the potential of engineered delivery vehicles that offer enhanced stability of loaded macromolecules from the biological environment and selectively deliver them at the desired site. Recent progress in nanoengineered lipid and polymeric-based delivery systems has broadened the scope of therapeutic targets of macromolecule drugs for various medical conditions. The approval of the first siRNA drug i.e. Patisiran (ONPATTRO™) for the management of transthyretin-regulated amyloidosis is a legendary breakthrough. In this review, we are broadly identifying the current challenges in macromolecule therapeutics and evaluating the advancements in engineered delivery systems for the delivery of biomacromolecules in recent years. We believe that these findings will certainly address the challenges and will encourage the design and development of efficient carrier systems for the delivery of protein/peptide/nucleic acids.

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