Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation

Author(s)

Freitas Mariano, Kelli Cristina ^[1] ; Boava Papini, Juliana Zampoli ^[2] ; de Faria, Naially Cardoso ^[3] ; Cabral Heluany, Daniele Nicoli ^[2] ; Lourenconi Botega, Ana Luiza ^[2] ; Saia Cereda, Cintia Maria ^[2] ; de Paula, Eneida ^[4] ; Tofoli, Giovana Radomille ^[2] ; de Araujo, Daniele Ribeiro ^{[1, 5]}

Affiliation

^[1] Fed Univ ABC, Human & Nat Sci Ctr, Santo Andre, SP - Brazil

^[2] Sao Leopoldo Mandic Res Inst, Sao Leopoldo Mandic Fac, Campinas, SP - Brazil

^[3] Univ Fed Sao Paulo, Translat Med Postgrad Program, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Dept Biochem, Campinas, SP - Brazil

^[5] Fed Univ ABC, Drugs & Bioact Delivery Syst Res Grp SISLIBIO, Av Estados, 5001 Bl A, T3, Lab 503-3 Bangu, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: BIOMED RESEARCH INTERNATIONAL; v. 2021, SEP 16 2021.
• Web of Science Citations: 0

Abstract

This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G/G `' = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R-2 = 0.923-0.989), indicating the drug diffusion from hydrogels to the medium. RVGPL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to similar to 340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period. (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