Liposome-based drug delivery systems for ropivacaine encapsulated by remote (pH and ion gradient) loading.

Abstract

Ropivacaine (RVC), an amino-amide local anesthetic (LA), has been increasingly used in clinical practice since 1985, withlower toxicity than bupivacaine (BVC), the drug of choice for surgical procedures. In the main line of investigation of our research group (Biomembranes, Biochemistry department, IB/Unicamp)i.e, preparation of sustained release systems for local anesthetics, this project intends to improve encapsulation, to prolong anesthesia time and to reduce the toxicity of ropivacaine, using liposomes with internal-external transmembrane gradient as well as a combination of (donor/acceptor) liposomes It should be noted that our group has been working in the development of new pharmaceutical forms for RVC in carriers such as PLGA nanospheres (Moraes et al. Intl. J. Pharm. 331:99, 2007), egg phosphatidylcholine/cholesterol liposomes (de Araújo et al., J. Pharm. Pharmacol., 60:1, 2008) and beta-cyclodextrins (de Araújo et al. Quim. Nova 31:1775, 2008) with promising results regarding the anesthesia effect, in animal models. In this study, liposomes prepared with ion gradients or in combination (donor/acceptor), will be tested in vitro and in vivo, and their effectiveness will be compared to the commercial RVC formulations currently available. Through a simple, inexpensive and innovative process, we intend to increase the loading of RVC into the liposomes, to extend anesthesia time and to reduce the toxicity of ropivacaine, aiming the clinical treatment of pain (in surgical and post-operative procedures) with a possible technological product.