Improved tacrolimus skin permeation by co-encapsulation with clobetasol in lipid nanoparticles: Study of drug effects in lipid matrix by electron paramagnetic resonance
| Autor: | Luís Antônio Dantas Silva, Ricardo Neves Marreto, Antonio Alonso, Stephânia Fleury Taveira, Priscila Bianca Rodrigues da Rocha, Jorge L.V. Anjos, Anna Paula Krawczyk-Santos, Isabella C. S. M. Amorim, Lígia Marquez Andrade, Eliana Martins Lima |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Swine Skin Absorption media_common.quotation_subject Pharmaceutical Science Nanoparticle chemical and pharmacologic phenomena 02 engineering and technology Administration Cutaneous 030226 pharmacology & pharmacy Tacrolimus law.invention Chitosan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine stomatognathic system law Animals Electron paramagnetic resonance media_common Clobetasol Drug Carriers Chromatography Chemistry Electron Spin Resonance Spectroscopy General Medicine Penetration (firestop) Permeation 021001 nanoscience & nanotechnology Lipids stomatognathic diseases Diffusion Chambers Culture Nanoparticles 0210 nano-technology Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 119:142-149 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2017.06.014 |
| Popis: | Combined therapy with corticosteroids and immunosuppressant-loaded nanostructured lipid carriers (NLC) could be useful in the treatment of skin diseases. To circumvent NLC loading capacity problems, loaded drugs should have different physicochemical characteristics, such as tacrolimus (TAC) and clobetasol (CLO). Therefore, in the present study, TAC and CLO were encapsulated in NLC (TAC-NLC, CLO-NLC and TAC+CLO-NLC), coated or otherwise with chitosan. Electron paramagnetic resonance (EPR) spectroscopy of different spin labels was used to investigate the impact of drug and oil incorporation on the lipid dynamic behavior of the lipid matrices. In addition, the impact of co-encapsulation on drug release and skin permeation was evaluated. Entrapment efficiency was greater than 90% for both drugs, even when the maximum drug loading achieved for TAC-NLC and CLO-NLC was kept at TAC+CLO-NLC, because TAC is more soluble in the solid lipid and CLO in the liquid lipid. EPR data indicated that both drugs reduced the lipid fluidity near the polar surface of the lipid matrix, which suggests their presence in this region. In addition, EPR data showed that liquid lipid is also present in more superficial regions of the nanoparticle matrix. CLO was released faster than TAC from TAC+CLO-NLC, probably because it is more soluble in the liquid lipid. TAC skin penetration was affected by CLO. A 5-fold increase in TAC penetration was observed from TAC+CLO-NLC when compared to TAC-NLC formulations. Coating also increased TAC and CLO permeation to deeper skin layers (1.8-fold and 1.6-fold, respectively). TAC+CLO-NLC seems to be an effective strategy for topical delivery of TAC and CLO, and thus constitutes promising formulations for the treatment of skin diseases. |
| Databáze: | OpenAIRE |
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