Can dermal delivery of therapeutics be improved using thermoresponsive nanogels?

Abstract

Skin, being the largest organ of the body, has attracted a lot of attention in recent years as a vector to deliver awide spectrum of cargo molecules to treat multiple conditions, including genetic disorders, infections by pathogens(bacteria, virus, fungus), inflammatory diseases such as psoriasis and atopic dermatitis, and skin cancer. In order todeliver active molecules across the skin layers, it is crucial to understand the morphology and properties of skin. Ahealthy skin is associated with a highly efficient barrier that prevents invasion of foreign particles or microbes fromthe external environment. As a consequence, the outermost layer of the epidermis, also called the stratum corneum(SC), prevents penetration of molecules that are larger than 500 Da [1]. This represents an immense challenge fordelivery of bigger active molecules into the skin tissues via passive diffusion. Various formulations such as creams,gels and ointments have been studied to overcome the skin protective barrier but they mainly intend to have localeffect rather than systemic action. To enhance penetration of active therapeutics across the skin, several techniqueshas been developed. This includes chemicals such as surfactants, alcohols, amines ? among others, or physicaldisruption of the SC using methods such as sonoporation, iontophoresis, electroporation and microneedles [2].Although penetration enhancers have proven to be effective for delivery of active therapeutics, they could leadto long-term or irreparable damage of the lipid structure of the SC. Nanogels, being cross-linked polymers withnanometer dimensions, provide an alternative approach to existing technologies with minimal damage to thenatural barrier function of the skin. Furthermore, nanogels possess certain desirable features such as solubility andstabilization of hydrophobic drugs or proteins and the ability to target encapsulated moieties to specific cell types,with control over release profiles. In addition, nanogels that respond to various stimuli such as pH and temperatureare shown to enhance the penetration of cargo molecules in the skin by interacting with the SC, followed by thetriggered release of cargo molecules [3?5].