Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis

• Published in: Scientific reports 2015-12, Vol.5 (1), p.18089, Article 18089
• Main Authors: Jung, Sang-Myung, Yoon, Gwang Heum, Lee, Hoo Chul, Jung, Moon Hee, Yu, Sun Il, Yeon, Seung Ju, Min, Seul Ki, Kwon, Yeo Seon, Hwang, Jin Ha, Shin, Hwa Sung
• Format: Article
• Language: English
• Subjects: 101/1; 13/107; 14/34; 38/77; 631/61/2035; 631/61/350/354; 631/61/54/152; 631/61/54/2295; Animals; Animals, Newborn; Atopic dermatitis; Cell Survival - drug effects; Cells, Cultured; Ceramide; Ceramides - chemistry; Chemokine CCL2 - genetics; Chitosan; Chitosan - chemistry; Controlled release; Cytotoxicity; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - genetics; Dermatitis, Atopic - physiopathology; Dermatologic Agents - chemistry; Dermatologic Agents - pharmacokinetics; Dermatologic Agents - pharmacology; Drug Design; Eczema; Fibroblasts - cytology; Fibroblasts - drug effects; Gene Expression - drug effects; Humanities and Social Sciences; Immunohistochemistry; Lactic Acid - chemistry; Microscopy, Electron; multidisciplinary; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - ultrastructure; pH effects; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Polylactide-co-glycolide; Psoriasis; Rats, Sprague-Dawley; Regeneration - drug effects; Regeneration - genetics; Reverse Transcriptase Polymerase Chain Reaction; Science; Side effects; Skin Absorption; Skin diseases; Solvents; Stratum corneum; Temperature effects; Thermodynamics; Transdermal medication; Tumor Necrosis Factor-alpha - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18089

Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD.