title: Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation.
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.
authors: Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil.
authors: Alessandra C S
authors: ACS
authors: Akkari
authors: São Francisco University, Bragança Paulista, São Paulo, Brazil.
authors: Juliana Z Boava
authors: JZB
authors: Papini
authors: Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil.
authors: Gabriella K
authors: GK
authors: Garcia
authors: Nuclear and Energy Research Institute, São Paulo, SP, Brazil.
authors: Margareth K K Dias
authors: MKKD
authors: Franco
authors: School of Chemical Engineering, University of Campinas, SP, Brazil.
authors: Leide P
authors: LP
authors: Cavalcanti
authors: Brazilian Synchrotron Light Laboratory, Campinas, SP, Brazil.
authors: Antonio
authors: A
authors: Gasperini
authors: Brazilian Synchrotron Light Laboratory, Campinas, SP, Brazil.
authors: Melissa Inger
authors: MI
authors: Alkschbirs
authors: Department Quantum Phenomena in Novel Materials Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Berlin, Germany.
authors: Fabiano
authors: F
authors: Yokaichyia
authors: Department of Biochemistry, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors: Eneida
authors: E
authors: de Paula
authors: Faculty of Dentistry São Leopoldo Mandic, Campinas, São Paulo, Brazil.
authors: Giovana R
authors: GR
authors: Tófoli
authors: Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil. Electronic address: daniele.araujo@ufabc.edu.br.
authors: Daniele R
authors: DR
authors: de Araujo
mesh_terms: D016475:3T3 Cells; D000772:Anesthesia, Local / Q000379:methods*; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008823:Micelles; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020100:Hydrogels; D008823:Micelles; D020442:Poloxamer
keywords: Hydrogel; Local anesthesia; Micelle; Poloxamer; Ropivacaine