Lipid-drug conjugates: a potential nanocarrier system for oral drug delivery applications

Abstract

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.

Formulation and Intracellular Trafficking of Lipid–Drug Conjugate Nanoparticles Containing a Hydrophilic Antitubercular Drug for Improved Intracellular Delivery to Human Macrophages

“…In Vitro Drug Release Study. The in vitro release of INH from LDC-NPs was determined by quantifying diffusion of the released drug through a dialysis membrane 50 using an 8station, automated dissolution test apparatus (Disso-8, Lab India, Mumbai, India). To simulate in vivo gastric conditions, the study was performed in simulated intestinal fluid (SIF, phosphate buffer, pH 7.4) as a dissolution test medium, using a dialysis membrane with a MWCO of 12 000 Da, activated by soaking in SIF for overnight.…”

Self-Emulsifying Drug Delivery Systems: Easy to Prepare Multifunctional Vectors for Efficient Oral Delivery

“…Lipid-drug conjugates (LDCs) are lipid nanoparticle formulations which are characterized by the conjugation ability of the lipid matrix with the hydrophilic drug moieties, and thus provide novel pro-drugs to achieve many therapeutic outcomes in oral drug delivery [18]. Like other lipid-based nanocarrier systems, LDCs possess several advantages including biocompatibility, being solid at body and room temperature, high capacity for loading hydrophilic drugs, high permeation through GI tract, enhanced drug absorption through lymphatic uptake, improving stability and bioavailability loaded drugs, and feasibility of large scale production [19].…”

Synthesis, Characterizations, and Use of O-Stearoyl Mannose Ligand-Engineered Lipid Nanoarchitectonics for Alveolar Macrophage Targeting

“…The percentage yield of OSM was estimated as the amount taken for D-(+)-mannose and stearic acid during the process of synthesis and calculated using the following formula adopted earlier for percentage yield estimation. 15,16 % yield = Actual amount of bulk OSM obtained the total amount of Dmannose + stearic acid ð Þ…”