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

Author(s)

Campos, Estefania V. R. ^{[1, 2]} ; Proenca, Patricia L. F. ^[3] ; da Costa, Tais Germano ^[4] ; de Lima, Renata ^[4] ; Hedtrich, Sarah ^[5] ; Fraceto, Leonardo Fernandes ^[3] ; de Araujo, Daniele Ribeiro ^{[1, 2]}

Affiliation

^[1] Fed Univ ABC, Human & Nat Sci Ctr, BR-09210580 Santo Andre, SP - Brazil

^[2] Fed Univ ABC, Drugs & Bioact Delivery Syst Res Grp SISLIBIO, BR-09210580 Santo Andre, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Sci & Technol, Dept Environm Engn, BR-18087180 Sorocaba, SP - Brazil

^[4] Univ Sorocaba UNISO, Lab Evaluat Bioact & Toxicol Nanomat, BR-18023000 Sorocaba, SP - Brazil

^[5] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3 - Canada

• Document type: Journal article
• Source: ACS APPLIED POLYMER MATERIALS; v. 3, n. 9, p. 4436-4449, SEP 9 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 19/05100-0 - Evaluation of the biological activity of topical formulations of budesonide in inflammatory skin models
• Grantee: Estefânia Vangelie Ramos Campos
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 19/20303-4 - Thermosensitive organogels as strategies for the treatment of inflammatory processes: from supramolecular structure to pharmacological evaluation
• Grantee: Daniele Ribeiro de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/24402-1 - pH AND TEMPERATURE SENSITIVE DRUG NANOCARRIERS FOR SKIN APPLICATIONS
• Grantee: Estefânia Vangelie Ramos Campos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral