Improved Dermal Delivery of Cyclosporine A Loaded in Solid Lipid Nanoparticles

• Published in: Nanomaterials (Basel, Switzerland) Vol. 9; no. 9; p. 1204
• Main Authors: Essaghraoui, Abderrazzaq, Belfkira, Ahmed, Hamdaoui, Bassou, Nunes, Cláudia, Lima, Sofia A Costa, Reis, Salette
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.08.2019; MDPI
• Subjects: Autoimmune diseases; Charge efficiency; Cyclosporins; Drug delivery systems; Entrapment; Fibroblasts; Fourier transforms; HaCaT cells; Keratinocytes; Lipids; Microemulsions; Nanoparticles; nanostructured lipid carriers; Oleic acid; peptide encapsulation; Peptides; pH effects; Pork; Psoriasis; Skin; Skin diseases; skin penetration/permeation; solid lipid nanoparticles; Surface charge; Surfactants; topical administration; Transdermal medication; United States > US; fibroblasts; HaCaT cells; peptide encapsulation; topical administration; solid lipid nanoparticles; nanostructured lipid carriers; skin penetration/permeation
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano9091204

Cyclosporine A (CsA) is an immunosuppressant frequently used in the therapy of autoimmune disorders, including skin-related diseases. Aiming towards topical delivery, CsA was successfully incorporated into lipid nanoparticles of Lipocire DM and Pluronic F-127 using the hot homogenization method. Two different nanocarriers were optimized: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) where oleic acid was the liquid lipid. The developed nanoparticles showed mean sizes around 200 nm, a negative surface charge, and drug entrapment efficiencies around 85% and 70% for SLNs and NLCs, respectively. The spherical CsA-loaded lipid nanoparticles were stable for 9 weeks when stored at room temperature, and exhibited in vitro pH-dependent release under skin mimetic conditions, following the Peppas-Korsmeyer model. CsA, when loaded in SLNs, was safe to be used up to 140 μg mL in fibroblasts and keratinocytes, while CsA-loaded NLCs and free drug exhibited IC values of 55 and 95 μg mL (fibroblasts) and 28 and 30 μg mL (keratinocytes), respectively. The developed SLNs were able to retain the drug in pork skin with a reduced permeation rate in relation to NLCs. These findings suggest that SLNs are a potential alternative to produce stable and safe CsA nanocarriers for topical administration.