LIPID-BASED NANOCARRIERS FOR THE LOCAL ANESTHETIC TETRACAINE

Abstract

The encapsulation of Local Anesthetics (LA) in ionic gradient liposomes (IGL) has been shown to increase the time of analgesia and decrease the side effects, by maintaining the drug in the site of action for a longer time. Intradermal administration of IGL prepared with (NH4)2SO4 in a human volunteer achieved up to 19, 38, and 48 h of successful anesthesia with 0.5, 1, and 2% bupivacaine respectively (Grant et al., Anesthesiol 101:133, 2004). Our group has recently reported large (up to 2%) amounts of LA ropivacaine (RVC) entrapped (%EE~70%) in egg PC/chol/alpha-tocopherol 4/3/0.07 mole % IGL with a sustained release (~25 h) (Silva et al., J Lip. Res.26:1, 2015; Plos One v.12 e0185828, 2017). Also, a significant increase in the sensory block duration (27 h) in rats was achieved with a 0.012% formulation of dibucaine in IGL (prepared with sulfate and citrate), in comparison to an equivalent DBC solution (11 h) (Couto et al., J. Pharm. Sci, in press, 2018). The aim of the present study is to develop a IGL for tetracaine (TTC), an aminoester LA extensively used in ophthalmology and topical anestesia. The formulation is expected to be suitable for the treatment of burn injuries (topical). We also intend to exploit another lipid-based nanocarrier systems, prepared with hydrogenated soy phosphatidyl-choline:TTC:NaCl. In that way we propose to prepare, to characterize and to test the activity of the lipid-based TTC formulations.