Protein nanocages for cutaneous delivery

Abstract

Skin is the largest organ of the human body which acts as the first line of defense against many external factors such as UV radiation, foreign particles, pathogens and allergens. The skin majorly consists of keratinocytes, in the epidermal layer at different stages of differentiation, along with extracellular matrix composed of cross-linked proteins and lipids. This tough matrix hinders the transport of drugs and other molecules into the skin. Drugs or cosmetic active ingredients for managing skin conditions are typically delivered trans-dermally and designed for slow and sustained release. These active ingredients are required to achieve the desired depth of penetration and have to act over a specific period without causing any side effects. However, this is seldom achieved. It has been observed that these active ingredients when delivered on to the skin, leads to complications such as depigmentation, irritation and dermatitis, due to the lack of specificity and penetration properties of conventional carrier molecules. Self-assembling protein nanocages forming hollow structures are explored as potential carriers in various nanotechnology applications. Nature-derived protein cages such as E2 (from Bacillus stearothermophilus E2 core domain of pyruvate dehydrogenase enzyme) and ferritin (from Archaeoglobus fulgidus) with intrinsic self-assembling properties have tunable structural and functional characteristics which can be engineered to suit various biological applications. In this work, E2 protein nanocages are engineered and used as shuttles for drug delivery to skin cells. Targeting and penetration peptides are genetically fused to these E2 nanocages for generating functionalized protein nanocages to enhance penetration through the skin layers and deliver active molecules to target-cells-of-interest, for the management of skin aging and hyperpigmentation.