posted on 2021-08-12, 14:09authored byEstefânia V. R. Campos, Patricia L. F. Proença, Tais Germano da Costa, Renata de Lima, Sarah Hedtrich, Leonardo Fernandes Fraceto, Daniele Ribeiro de Araujo
Atopic
dermatitis (AD) is a chronic, relapsing inflammatory skin
disorder characterized by intense itching and recurrent eczematous
lesions. Topical corticosteroids are the first-line 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.