Structure-function relationships in the modification of liposomes for targeted drug delivery in infectious diseases

Abstract

The introduction of liposomes has caused a paradigm shift in medicine, offering novel solutions to problems that are ancient to the drug discovery and development for HIV, TB, and malaria. These are the three deadliest infectious diseases that are endowed with complex pathophysiological and biological mechanisms that allow them to thrive in their hosts through escaping the immune system and capturing key pathways. Disease heterogeneity and lack of suitable models to replicate the disease states make compounds the poor pharmacokinetic issues associated with these diseases. Liposomes are lipid-based nanocarriers that are employed for drug formulations, preservation, and storage. Importantly, they can be tailored for targeted and controlled release. Structure–function relationships are crucial to consider in liposome design as they affect key interactions between the carrier drug and the target cell, which impact on drug release, cellular uptake, bioavailability, biodistribution, and toxicity. Herein, lipid composition, size, lamellarity, zeta potential/charge as well as surface modification with cholesterol, PEG, peptides, and antibodies are discussed with respect to selectivity in targeting diseased cells. The role of computational tools in expediting the liposome technology is reviewed, highlighting the impact of forces of interaction between biomolecules and the conditions of the environment.