Pluronics F-127/L-81 Binary Hydrogels as Drug-Delivery Systems: Influence of Physicochemical Aspects on Release Kinetics and Cytotoxicity

Abstract

We investigated the structure of the binary mixture of Pluronic F-127 (PL F-127) and Pluronic L-81 (PL L-81), as hydrogels for sumatriptan delivery and investigated the mixture possible use via subcutaneous route for future applications as a long-acting antimigraine formulation. We studied the drug-micelle interaction by dynamic light scattering and differential scanning calorimetry, sol-gel process by rheology, and small-angle X-ray scattering (SAXS). We also employed pharmaceutical formulation aspects by dissolution rate, release profile, and cytotoxicity studies for apoptosis and/or necrosis in fibroblasts (3T3) and neural cells (Neuro 2a). Micellar hydrodynamic diameter studies revealed the formation of binary PL-micelles by association of PL F-127/PL L-81. The mixed micelle and binary hydrogels formation was also verified by only one phase transition temperature for all formulations, even in the presence of sumatriptan. The characterization of the hydrogel supramolecular organization by SAXS, rheology studies, and in vitro dissolution/release results showed a probable relationship between the transition of the lamellar to the hexagonal phase and the lower release constant values observed, indicating that PL L-81 participates in micelle-hydrogel formation and aggregation processes. Furthermore, the reduced cytotoxicity (annexin V-fluorescein isothiocyanate positive staining), with minor PL L-81 concentration, points to its potential use for the development of binary PL-systems containing sumatriptan capable of modulating the gelation process. This use may employ the minimum PL concentration and be interesting for pharmaceutical applications, particularly for migraine treatment.

Budesonide-hydroxypropyl-β-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels

“…The BUD release kinetic constant values were determined considering zero order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas mathematical models. For the systems composed of PL 407, the best fit was found to be the Higuchi model (0.964 ≤ R 2 ≤ 0.986), indicating the drug transport by diffusion according to the Fick's law [48], for both colonic fluids (Table 4), as also observed for PL 407 after incorporation of different drugs such as tramadol [20], lidocaine [49] and sumatriptan [19].…”

“…Table 2 presents the micellar mean hydrodynamic diameter and the average size distribution for the different systems studied (PL407 and PL407-PL403) at room temperature (25 • C) and body temperature (37 • C). Even those PL systems did not form hydrogels (at 4% w/w) the analysis was important to simulate the micelles behavior, when in contact with the physiological temperature, after hydrogels dissolution [19,20].…”

In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models

“…It is worth noting that at body temperature the G ʹʹ value of GEL1 became obviously lower than that of GEL2. It is known that the gelation capability of poloxamer solutions depends closely on the polymer concentration22, 23, 24. Our result indicated that both the two formulations had adequate anti-dilution capacity, assuring that they could form hydrogels after administration in the vagina even after dilution by vaginal fluid.

Figure 3Effect of dilution on the gelation process of the hydrogel formulations (5 mL) with 0.5 mL (A and B) or 0.75 mL (C and D) simulated vaginal fluid.

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A nano-cocktail of an NIR-II emissive fluorophore and organoplatinum(ii) metallacycle for efficient cancer imaging and therapy

“…2e). 54,55 PSY exhibited high photo-stability with negligible decay compared with the FDA-approved NIR-I theranostic agent indocyanine green (ICG) under continuous irradiation at 808 nm for 1 h (Fig. 2f).…”