Self-Nanoemulsifying Drug Delivery Systems for Cardiovascular Therapeutics: Formulation Strategies, Pharmacokinetic Enhancement and Precision-Oriented Translation.

Cardiovascular drugs face many barriers to oral delivery, and self-nanoemulsifying drug delivery systems (SNEDDS) are becoming a promising nano-enabled drug delivery vehicle to address these challenges and aid precision cardiovascular delivery. The poor aqueous solubility and/or intestinal permeability, combined with high intestinal and hepatic clearance and, in some cases, intestinal P-glycoprotein (P-gp) efflux, leads to variable systemic exposure and inconsistent therapeutic activity of many antihypertensive drugs, antianginal drugs, and cardioprotective agents. Under gastrointestinal dilution conditions, SNEDDS spontaneously generate nanosized oil-in-water emulsions that keep drugs in a solubilized state, promote drug dissolution, enhance membrane interactions, increase intestinal permeability levels due to surfactant activity, reduce membrane fluidization by P-glycoprotein mediated efflux, increase lymphatic transport, decrease hepatic first pass metabolism, and decrease pharmacokinetic variability. This allows for more predictable pharmacokinetic performance, reduced interpatient variability, therapeutic optimization, and therefore an enabling concept of nano-enabled precision cardiology. This graphical abstract depicts the importance of self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing drug absorption, providing enhanced bioavailability, increasing drug absorption and pharmacokinetic predictability, and facilitating precision cardiovascular therapy by overcoming the oral bioavailability barriers.