Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation

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Akkari, Alessandra C. S. ; Boava Papini, Juliana Z. ; Garcia, Gabriella K. ; Dias Franco, Margareth K. K. ; Cavalcanti, Leide P. ; Gasperini, Antonio ; Alkschbirs, Melissa Inger ; Yokaichyia, Fabiano ; de Paula, Eneida ; Tofoli, Giovana R. ; de Araujo, Daniele R.

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 68, p. 299-307, NOV 1 2016.
• Web of Science Citations: 20

Abstract

In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/26200-9 - Nanostructured hybrid systems for modified release of antiinflammatpry drugs: development and pharmacological evaluation
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants
• 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