Hydrogels Containing Budesonide-Loaded Nanoparticles to Facilitate Percutaneous Absorption for Atopic Dermatitis Treatment Applications

Abstract

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense itching and recurrent eczematous lesions. Topical corticosteroids are the firstline treatment to control moderate-to-severe AD; however, prolonged application of corticosteroids is required, which can result in dermal atrophy as a side effect. Drug-delivery systems can provide more effective and targeted therapy strategies. In this study, budesonide (BUD) was encapsulated into chitosan (CS)coated PLGA nanoparticles, which were further incorporated into poloxamer hydrogels to improve the anti-inflammatory activity and decrease adverse effects. The nanoparticles were prepared by the emulsification−solvent evaporation technique, and their physicochemical characteristics were evaluated. Rheological properties of the hydrogels, such as viscosity and sol−gel transition temperature, were evaluated with and without nanoparticles. In vitro release kinetics and ex vivo drug absorption studies were performed using Franz diffusion cells. The nanoparticles showed a mean diameter of 324 ± 4 nm, positive ζ potential (20 mV) due to CS coating, and high encapsulation efficiency (>90%). The nanoparticles did not show cytotoxic effects in primary human fibroblasts and keratinocytes; however, all formulations induced the generation of reactive oxygen species. Both nanoparticles and hydrogels were able to change the release kinetics of BUD when compared to the nonencapsulated compound. Nanoparticles were not able to surmount the stratum corneum of excised human skin, but the nanoencapsulation facilitated the skin absorption of BUD. The hydrogels containing nanoparticles or not showed non-Newtonian and pseudoplastic behavior. The nanoformulations seem to be a good candidate to deliver glucocorticoids in the skin of AD patients.

Hydrogel dressing integrating FAK inhibition and ROS scavenging for mechano-chemical treatment of atopic dermatitis

“…Finally, the hydrogels must have good tissue adhesion to ensure stable residence on the skin and avoid the use of additional tape or gauze. Although some previous works have used hydrogels as AD skin dressings to deliver therapeutic factors 29 , 30 , these hydrogels often fail to meet the specific needs of AD management.…”

Study of the Synergistic Immunomodulatory and Antifibrotic Effects of Dual-Loaded Budesonide and Serpine1 siRNA Lipid–Polymer Nanoparticles Targeting Macrophage Dysregulation in Tendinopathy

“…BUD is a corticosteroid that has been described to switch macrophages to the M2 phenotype in other therapeutic applications . Even if budesonide has been ascribed some long-term side effects, the delivery of this drug with LPNs allows us to reduce the dose needed for therapeutic efficacy and to avoid repeated administrations. ,, Hence, the potential of BUD loaded in LPNs to shift macrophages from an M1 inflammatory profile to the pro-regenerative M2 phenotype was evaluated by analyzing the expression of the M1 marker CD86 and the M2 marker CD206 by antibody staining and flow cytometry analysis following the gating strategy in Scheme S1. In addition, changes in the release of the pro-inflammatory cytokine IL-1β and changes in the release of the anti-inflammatory cytokine IL-4 were studied by enzyme-linked immunosorbent assay (ELISA) in the supernatants collected.…”

Challenges of current treatment and exploring the future prospects of nanoformulations for treatment of atopic dermatitis

“…In a different study, Campos et al [ 75 ] encapsulated the anti-inflammatory drug budesonide (BUD) in chitosan (CS)-coated PLGA nanoparticles, which were incorporated into poloxamer hydrogels to enhance anti-inflammatory efficacy and reduce side effects [ 75 ]. The nanoparticles were prepared using the emulsification solvent evaporation method and showed no adverse effects on primary human fibroblasts and keratinocytes.…”