RESUMEN

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. RVC-PL 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 ~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.

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RESUMEN

Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid-Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic-lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle-micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G'/G" relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm-2) compared to OA-PL F-127 (3.51 µg.cm-2) and OA (2.25 µg.cm-2) or hydrogels (∼1.2 µg.cm-2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml-1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration.

RESUMEN

The aim of this study was to synthesize a novel drug delivery system using organogels (ORGs) and characterize its physicochemical properties, in vitro and ex vivo permeation abilities, cytotoxicity and in vivo local anesthetic effects. The ORG formulations contained a mixture of oleic acid-lanolin (OA-LAN), poloxamer (PL407), and the commonly used local anesthetic lidocaine (LDC). The main focus was to evaluate the impact of LAN and PL407 concentrations on the ORG structural features and their biopharmaceutical performance. Results revealed that LDC, OA, and LAN incorporation separately shifted the systems transitions phase temperatures and modified the elastic/viscous moduli relationships (G'/G″ = ~15×). Additionally, the formulation with the highest concentrations of LAN and PL407 reduced the LDC flux from ~17 to 12 µg·cm-2·h-1 and the permeability coefficients from 1.2 to 0.62 cm·h-1 through ex vivo skin. In vivo pharmacological evaluation showed that the ORG-based drug delivery system presented low cytotoxicity, increased and prolonged the local anesthetic effects compared to commercial alternatives. The data from this study indicate that ORG represent a promising new approach to effectively enhance the topical administration of local anesthetics.

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