Therapeutic Effects of 30 nm Cyclosporin A-Loaded Nanoparticles Using PLGA-PEG-PLGA Triblock Copolymer for Transdermal Delivery in Mouse Models of Psoriasis

Abstract

This study aimed to evaluate the effectiveness of poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) as a drug carrier in the treatment of psoriasis. Nanoparticles containing cyclosporin A (CsA) were prepared, and their cytotoxicity and skin irritation properties were investigated. These results revealed that the nanoparticles themselves had no obvious cytotoxicity or skin irritation effects. Furthermore, it was shown that loading CsA into nanoparticles promoted its cellular uptake. The therapeutic effect of CsA-loaded PLGA-PEG-PLGA nanoparticles on psoriasis was evaluated using a mouse model of psoriasis induced by imiquimod. In psoriatic skin, we confirmed that nanoparticles penetrate deep into the skin. Furthermore, it was suggested that by using PLGA-PEG-PLGA, drug carriers could reach the dermal layer, which is the target site for psoriasis treatment. The observation of skin sections after the treatment experiment showed that excessively proliferated keratinocytes were restored to an almost normal state by using PLGA-PEG-PLGA nanoparticles as drug carriers. Additionally, the quantitative measurement results for cytokines revealed that the levels of TNF-α, IL-17A, and IL-22 were significantly decreased compared with those of the group to which CsA suspended in a 20% ethanol solution was administered. These results indicate that PLGA-PEG-PLGA nanoparticles are promising drug carriers for the transdermal administration of CsA.

Keywords

• transdermal delivery
• cyclosporin A
• nanoparticle
• PLGA-PEG-PLGA
• PLGA
• psoriasis