Lipid Drug Conjugates for Improved Therapeutic Benefits

Abstract

Lipid drug conjugates (LDCs) are the chemical entities, which are commonly referred to as lipoidal prodrug. They contain the bioactive molecules, covalently or non-covalently linked with lipids like fatty acids, glycerides or phospholipids. Lipid drug conjugates are fabricated with the aim of increasing drug payload. It also prevents leakage of a highly polar bioactive(s) from the lipophilic matrix. Conjugating lipidic moieties to bioactive molecules improves hydrophobicity. It also modifies other characteristics of bioactive(s). These conjugates possess numerous merits encompassing enhanced tumor targeting, lymphatic system targeting, systemic bioavailability and decreased toxicity. Different conjugation approaches, chemical linkers and spacers can be used to synthesize LDCs based on the chemical behaviour of lipidic moieties and bioactive(s). The factors such as coupling/ conjugation methods, the linkers etc. regulate and control the release of bioactive(s) from the LDCs. It is considered as a crucial parameter for the better execution of the LDCs. The purpose of this review is to explore widely the potential of LDCs as an approach for improving the therapeutic indices of bioactive(s). In this review, the conjugation methods, various lipids used for preparing LDCs, and advantages of using LDCs are summarized. Though LDCs might be administered without using a carrier; however, majority of them are incorporated in an appropriate nanocarrier system. In the conjugates, the lipidic component may considerably improve the loading of lipoidal bioactive(s) in the lipid compartments. This results in high % drug entrapment in nanocarriers with greater stability. Several nanometric carriers such as polymeric nanoparticles, micelles, liposomes, emulsions and lipid nanoparticles, which have been explored, are reviewed here.