Opportunities and challenges of fatty acid conjugated therapeutics

Abstract

Instability, poor cellular uptake and unfavorable pharmacokinetics and biodistribution of many therapeutic molecules require modification in their physicochemical properties. The conjugation of these APIs with fatty acids has demonstrated an enhancement in their lipophilicity and stability. The improvement in the formulations that resulted from the conjugation of a drug with a fatty acid includes increased half-life, enhanced cellular uptake and retention, targeted tumor delivery, reduced chemoresistance in cancer, and improved blood-brain-barrier (BBB) penetration. In this review, various therapeutic molecules, including small molecules, peptides and oligonucleotides, that have been conjugated with fatty acid have been thoroughly discussed along with various conjugation strategies. The application of nano-system based delivery is gaining a lot of attention due to its ability to provide controlled drug release, targeting and reducing the extent of side effects. This review also covers various nano-carriers that have been utilized for the delivery of fatty acid drug conjugates. The enhanced lipophilicity of the drug-fatty acid conjugate has shown to enhance the affinity of the drug towards these carriers, thereby increasing the entrapment efficiency and formulation performance.