Nanocarriers for tailored skin delivery: More than just the carriers?

Abstract

Skin diseases are among the top 5 most leading diseases causing non-fatal health burden worldwide and strategies to assure more effective treatments are urgently needed. Dermal therapy is very attractive due to the direct administration of the drug at the diseased skin site thus minimizing systemic side effects associated with the oral and parenteral routes. However, the great variety within the skin conditions can be a challenge in the development of effective dermal therapies. Based on the skin disease, the drug action is often required at different depths within the skin. The failure to penetrate the skin layers might result in sub-therapeutic drug levels at the targeted skin site and unsuccessful treatments. Phospholipid-based nanocarriers have great potential to overcome the current limitations in dermal therapy by assuring controlled and sustained drug delivery and promoting drug/substance transport in the deeper skin layers. The nanocarrier properties can be tailored and exploited to optimize skin drug delivery. In the present study we optimized nanocarriers for tailored skin drug delivery. A closer-to-in vivo skin penetration model was developed to select nanocarriers with specific skin-targeted drug delivery potential. Deformable liposomes were found the most promising nanocarriers delivering model substances in the deeper skin layers while avoiding systemic absorption. Further optimization of the selected nanocarrier was performed by exploring the effect of the liposomal surface charge on dermal delivery. The sustained skin penetration of drug/active substances for liposomally-associated drugs/substances was influenced by both the liposomal surface charge and physicochemical properties of the nanocarrier-associated drug/substance. The enhancement of the biological activities of both human epidermal growth factor and curcumin when incorporated in the liposomal system as compared to both active substances in solutions was found to be dependent on the liposomal surface charge. Positively charged deformable liposomes embedded in chitosan hydrogel enabled stable bioadhesive hydrogel providing a sustained skin penetration of curcumin. The developed liposomal hydrogel formulation has a potential to be further evaluated as advanced wound dressing.