Ultra‐Long‐Duration Local Anesthesia Produced by Injection of Lecithin‐Coated Tetracaine Microcrystals

Abstract

This study was designed to determine if microencapsulated tetracaine would provide a longer duration of local anesthesia than nonmicroencapsulated (neat) tetracaine. Local anesthesia was determined by monitoring the response of the rat to tail clamping after the installation of a subcutaneous ring block. Ten percent microencapsulated tetracaine was found to provide local anesthesia of the tail for a 43-hour duration. Ten percent tetracaine solution was toxic. One percent tetracaine solution provided a tail block lasting 8 hours. Lecithin membranes without drug provided no block. This study demonstrates that lecithin-coated tetracaine microcrystals produce a local anesthetic effect that is ultra-long in duration, reversible, and not systemically toxic.

A Review about various Nanomaterials in Drug Delivery Systems and their Applications

“…It deals with higher load s o f particulates in nanosuspension formulation as well as admissibility of particulates of size more than 40 μm from products like them [16]. Boedeker et al, (1994) explored the anaesthetic effect of a lecithin-coated tetracaine-HI nanosuspension. Sonication method was employed to prepare the nanoparticulates, where 80% of particulates were found to be within size range of 100 to 500 nm while none of particulate was >5 μm.…”

“…No anaesthetic effect was revealed in negative controls of lecithin sheaths without drug and 5% dextrose. Nanosuspensions receiving groups did not indicated any gross native tissue destruction or systemic toxicity [17]. Karan et al, (1996) studied treatment of malignant hyperthermia using Phospholipid-coated nanosuspensions of dantrolene and sodium dantrolene.…”

Absorption and Physicochemical Properties of the NCE

“…Reducing the particle size increases the surface area available to the dissolution media and increases the overall apparent dissolution rate. The use of nanoparticles for the delivery of poorly water-soluble drugs has been increasingly used [36,[38][39][40][41][42][43][44][45][46]. In addition to dissolution improvements, nanolized particles offer advantages such as GI retention [51], and solubility improvements.…”

Local Toxicity from Local Anesthetic Polymeric Microparticles

“…A very broad range of controlled release formulations have been developed to provide prolonged duration local anesthesia, including polymeric microspheres, [1][2][3][4][5][6][7] surgically implantable pellets, 8 microcrystals, 9 liposomes, [10][11][12][13][14][15] (including a formulation undergoing human clinical trials 16,17 ) lipospheres, 18 cross-linkable hyaluronic acid matrices, 19 lipidprotein-sugar particles, 20,21 cyclodextrin complexes, 22,23 liposomes loaded with cyclodextrin complexes 24 and implantable membrane matrices. 25,26 Such systems have extended the duration of nerve block to varying degrees ranging from hours to weeks, but have not been widely adopted clinically.…”

“…32,[38][39][40] Reporting of local tissue injury from local anesthetic controlled release formulations has been variable, in both animal and human studies. Most do not describe myotoxicity [2][3][4][5][7][8][9][11][12][13][14][15]18,[22][23][24] (including the liposomal formulation undergoing human trials 16,17 ), while some others document mild muscle injury comparable to single injections of unencapsulated drug. 10,25,26 In our own work, we have found muscle injury to be a ubiquitous finding in a wide range of extended-release bupivacaine formulations independent of the delivery vehicle 6,19,21,41 or co-encapsulated agent, 32,37,42,43 and it is sometimes severe.…”