Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation

Abstract

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin’s biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.

A Novel Approach for Dermal Application of Pranoprofen-Loaded Lipid Nanoparticles for the Treatment of Post-Tattoo Inflammatory Reactions

“…This investigation discloses sufficient evidence that targeting and a prolonged effect can be accomplished with immense perspective in dermal delivery. Regarding the results obtained from the predicted steady-state plasma concentrations of PRA (Css) for both PRA-NLC and the PRA solution, assuming an area of application of 100 cm 2 of skin, they were far below the reported therapeutic plasma concentration achieved through oral administration (4.89 ± 1.29 µg/mL and 10.19 ± 2.43 µg/mL for older and younger humans, respectively) [39][40][41]. These values guarantee that the dermal application of the nanosuspension would not have any systemic effect; thus, they guarantee a safe local anti-inflammatory and analgesic effect.…”

“…The results of the permeation parameters-flux (J ss , µg/h/cm 2 ), permeability coefficient (Kp, cm/h), lag time (TL, h), the cumulative amount of PRA permeated after 24 h of experiment (Q 24h µg), and the amount retained in the skin (Q ret µg/g/cm 2 )-are described in Table 6. Table 7 shows the predicted steady-state plasma concentrations (C ss , µg/mL), the values of which were below the reported therapeutic plasma concentration (4.89 ± 1.29 µg/mL for older humans and 10.19 ± 2.43 µg/mL for younger humans) [39][40][41]. These results suggest that the dermal application of PRA-NLC may not have systemic effects, which guarantees a safe local anti-inflammatory and analgesic effect of the PRA.…”

“…where Jss is the flux, SAT is the hypothetical area of application (assuming an area of application of 100 cm 2 ), and CLp is the human plasma clearance value of PRA, which, according to literature, is 609.00 cm 3 /h for older people and 1146.60 cm 3 /h, for younger people [39][40][41].…”

Quality by Design of Pranoprofen Loaded Nanostructured Lipid Carriers and Their Ex Vivo Evaluation in Different Mucosae and Ocular Tissues

“…Table 13 shows the plasma concentration that would be achieved in the steady-state after the application of PF-NLCs-N6 on 1 cm 2 of porcine mucous membrane (buccal, sublingual, nasal and vaginal) and ophthalmic tissues (sclera and cornea). The predicted Css values were below the therapeutic concentrations in plasma 4.89 ± 1.29 µg/mL for young subjects and 10.19 ± 2.43 µg/mL for elderly subjects [ 25 ].…”

Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features

“…To measure, the electrode, a small hollow cylinder, was maintained on the different tissue’s surface for 1 min. TEWL values (g/m 2 ·h) were expressed as the mean ± SD of 10 replicates before and after the application of the formulations for at least 2 h. All measurements were carried out in accordance with published procedures [ 53 , 54 ].…”