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

Abstract

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.

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

“…In the nanocarrier literature reviewed here, only two-thirds of the articles mentioned nanocarrier toxicity. Most articles referred to previous work using in vitro models, while some performed their own toxicity screening in vitro using either human fibroblasts or keratinocytes, and examining cell death as the only metric [ 103 , 107 , 110 , 118 , 123 , 124 , 127 ]. Some researchers also examined gross toxicity and potential irritant effects [ 95 , 96 , 112 ], and Pople et al performed the most comprehensive toxicity assessment with a 28-day toxicity study that examined multiple target organs for histological abnormalities [ 98 ].…”

“…Another potentially novel treatment for skin diseases are ceramides, a component of the lipid structure in healthy stratum corneum. Jung et al successfully loaded ceramides into 200-nm chitosan nanoparticles and used them to treat a sodium dodecyl sulfate (SDS)-induced model of atopic dermatitis in rats [ 118 ]. Following treatment with ceramides in the nanocarrier, they observed stratum corneum repair in the rat model.…”

Nanosuspension-Based Dissolving Microneedle Arrays for Intradermal Delivery of Curcumin

“…The distribution of curcumin in full thickness neonatal porcine skin was investigated ex vivo using a cryostatic microtome, as described previously [22]. The full thickness neonatal porcine skin was excised and treated as above.…”

Recent Advances on Topical Application of Ceramides to Restore Barrier Function of Skin

“…Considering the chemical structure of CERs, they are highly lipophilic compounds because the ratio of long-chain fatty acids to the hydrophilic head part is high. As such, CERs are poorly water-soluble compounds [24]. Also, CERs are compounds with high molecular weight [25].…”