Stability and Local Toxicity Evaluation of a Liposomal Prilocaine Formulation

Abstract

This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLC_LUV) formulation () before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole %). Laser light-scattering analysis (p > 0.05) and thiobarbituric acid reaction (p > 0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by ¹H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLC_LUV, sterilized or not, up to 30 days after preparation (p > 0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLC_LUV. PLC_LUV did not evoke rat paw edema (p > 0.05), and no significant differences were found in histological analysis, when compared to the control groups (p > 0.05). The present work shows that PLC_LUV is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safety and possible clinical use in dentistry.

Keywords:

• local anesthetic
• prilocaine
• liposome
• drug delivery

Acknowledgements

The authors thank PhD Dr. Maria Silvia Viccari Gatti for her contribution in the microbiologic tests; Mr. Márcio Paschoal and Ms. Daniela Ceratti for their technical assistance; and Cristália Prod. Quim. Farmac. Ltda for the PLC samples and for the pyrogen tests. C.M.S.C. and E.P. received fellowships from CAPES (Comissão de Aperfeiçoamento de Pessoal do Ensino Superior) and CNP_q (Conselho Nacional de Desenvolvimento Cientifico e Technológico), respectively. This work was supported by FAPESP (Proc. 06/00121–9).