Hydrophilic drugs are preferred candidates for most routes of drug administration, because of their enhanced solubility and dissolution under aqueous in vivo conditions. However, their hydrophilic nature also leads to decreased permeability across hydrophobic barriers. This is a severe limitation in situations where membrane permeability is the primary factor affecting bioavailability and efficacy of the drug. Highly impermeable cellular membranes or the tight endothelial junctions governing the blood-brain barrier are prime examples of this limitation. In other cases, decreased permeability across mucosal or epithelial membranes may require increased doses, which is an inefficient and potentially dangerous workaround. Covalent conjugation of hydrophilic drugs to hydrophobic moieties like short-chain lipids is a promising strategy for maintaining the critical balance between drug solubility and permeability. This article practically focuses on the production procedure of Lipid drug conjugates (LDCs), various formulation methodologies for preparing LDC nanoparticles with detailed about their in vitro physicochemical characterization at laboratory scale. Moreover, brief overviews on the role of LDCs in novel drug delivery applications as a substrate to various disease therapies are provided. Graphical Abstract Three dimensional (3-D) schematic representation of LDCs structures.
Keywords: Drug delivery; Hydrophilic drug; Lipid drug conjugates; Oral administration.