Journal
ACS APPLIED POLYMER MATERIALS
Volume 3, Issue 9, Pages 4436-4449Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsapm.1c00021
Keywords
budesonide; polymeric nanoparticles; thermoresponsive hydrogels; atopic dermatitis; topical release
Funding
- Sao Paulo State Research Foundation (FAPESP) [2017/24402-1, 2019/05100-0, 2019/20303-4]
- National Council for Scientific and Technological Development (CNPq) [307718/2019-0]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [19/20303-4, 17/24402-1] Funding Source: FAPESP
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The study demonstrated that nanoparticles and hydrogels can alter the release kinetics of budesonide (BUD), leading to more effective treatment of atopic dermatitis (AD) and facilitating the skin absorption of BUD; while nanoparticles were unable to penetrate the stratum corneum, they were effective in promoting BUD absorption into the skin.
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 zeta 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.
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