Lipid-based carriers for the delivery of local anesthetics

There is a clinical need for pharmaceutical dosage forms devised to prolong the acting time of local anesthetic (LA) agents or to reduce their toxicity. Encapsulation of LA in drug delivery systems (DDSs) can provide long-term anesthesia for inpatients (e.g. in immediate postsurgical pain control, avoiding the side effects from systemic analgesia) and diminished systemic toxicity for outpatients (in ambulatory/dentistry procedures). The lipid-based formulations described here, such as liposomes, microemulsions, and lipid nanoparticles, have provided several nanotechnological advances and therapeutic alternatives despite some inherent limitations associated with the fabrication processes, costs, and preclinical evaluation models.

A description of the currently promising lipid-based carriers, including liposomes, microemulsions, and nanostructured lipid carriers, followed by a systematic review of the existing lipid-based formulations proposed for LA. Trends in the research of these LA-in-DDS are then exposed, from the point of view of administration route and alternatives for non-traditionally administered LA molecules.

Considering the current state and potential future developments in the field, we discuss the reasons for why dozens of formulations published every year fail to reach clinical trials; only one lipid-based formulation for the delivery of local anesthetic (Exparel®) has been approved so far.