Solid Lipid Nanoparticles for Dibucaine Sustained Release

Author(s)

Barbosa, Raquel de M. ^{[1, 2]} ; Ribeiro, Ligia N. M. ^[1] ; Casadei, Bruna R. ^[1] ; da Silva, Camila M. G. ^[1] ; Queiroz, Viviane A. ^[1] ; Duran, Nelson ^[3] ; de Araujo, Daniele R. ^[4] ; Severino, Patricia ^[5] ; de Paula, Eneida ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Biochem & Tissue Biol Dept, BR-13083862 Campinas, SP - Brazil

^[2] UNINASSAU Natal Coll, Pharm Dept, BR-59080400 Natal, RN - Brazil

^[3] Univ Estadual Campinas, Unicamp, Inst Chem, BR-13083861 Campinas, SP - Brazil

^[4] Fed Univ ABC, Human & Nat Sci Ctr, BR-09210580 Santo Andre, SP - Brazil

^[5] Inst Technol & Res, Av Murilo Dantas 300, BR-49032490 Aracaju, SE - Brazil

• Document type: Journal article
• Source: PHARMACEUTICS; v. 10, n. 4 DEC 2018.
• Web of Science Citations: 4

Abstract

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 degrees C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (similar to 72-89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants