Pre-clinical evaluation of new dibucaine formulations for preventive analgesia

Author(s)

Furlan, Beatriz ^[1] ; de Melo, Beatriz T. ^[1] ; Papini, Juliana Z. B. ^[1] ; Sperandio, Marcelo ^[1] ; Oliveira, Juliana D. ^[2] ; de Paula, Eneida ^[2] ; Cereda, Cintia M. S. ^[1] ; Tofoli, Giovana R. ^[1]

Affiliation

^[1] Inst Pesquisa Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Rua Jose Rocha Junqueira 13, BR-1304575 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Bioquim, Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Liposome Research; v. 31, n. 3, p. 230-236, JUL 3 2021.
• Web of Science Citations: 0

Abstract

We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical safety and effectiveness of this novel ionic liposomal formulation of dibucaine (DBC), as described in previous work. Effectiveness was evaluatedin vivoon Wistar rats (n = 8) that received plain DBC or liposomal DBC (DBCLUV). Control empty liposomes (without DBC) or saline were also used as control. Sciatic nerve block was performed using the formulations or controls (0.4 mL). A hindpaw incision-based postoperative pain model was used to evaluate mechanical hypersensitivity with von Frey filaments. To verify antiinflamatory activity protein levels of TNF-alpha, IL-1 beta, substance P and CGRP were measured by ELISA in the hindpaw tissue after 1 and 6 hours of the incision. To corroborate drug safety, sciatic nerve Schwann cell cultures were treated with the aforementioned formulations and assessed for cell viability (MTT assay) and death (flow cytometry assay). Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. All animals presented post incisional hypersensitivity and DBC(LUV)showed longer analgesic effect (p < 0.001). DBC(LUV)reduced TNF-alpha and CGRP levels (p < 0.05). Histopathological evaluation showed greater inflammatory reaction after the administration of control liposomes when compared to DBC (p < 0.05). There was no difference in Schwann cell viability and death between plain and encapsulated DBC. DBC(LUV)was safe and enhanced anaesthesia duration due to slow release of dibucaine from ammonium sulphate gradient loaded liposomes. (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