Micro‐ and Nanosystems for Advanced Transdermal Delivery

Abstract

The skin is the largest and most accessible organ in the human body and, as such, it appears as the most convenient portal for drug delivery. However, the skin is also a formidable barrier which, while protecting us from physical, chemical, and immunological agents, requires appropriate technology for effective delivery. Today, the most effective administration method for large, lipophobic, and polar molecules continues to be hypodermic injection, which is associated with pain, needle phobia, and stick injury. As an alternative, a range of advanced strategies to overcome the skin barrier have been established over the last few decades including chemical enhancement, sonophoresis, iontophoresis, electroporation, thermal ablation, and mechanical approaches. Encouraged by the advances in nanotechnology, micro-and nanosystems have emerged as powerful tools to overcome the skin barrier, enabling significant advances on the existing methods. In particular, microneedle-and nanoparticle-assisted transdermal delivery has gained significant traction and will most likely have a strong impact in the field. In this review, the most recent progress in the field of transdermal delivery based on microneedle and nanoparticle delivery systems is discussed and examples of key therapeutic application are provided. Finally, a critical summary is presented alongside a vision for future research directions.

Emerging skin-targeted drug delivery strategies to engineer immunity: A focus on infectious diseases

“…Despite the attractive advantages of cutaneous vaccination over prevailing immunization routes, the skin has been an underutilized organ for clinical immunization largely due to the lack of effective drug delivery systems that can enable safe, reproducible, and patient-friendly deployment of antigens to skin microenvironments [64,[68][69][70][71]. Palpably, the stratum corneum, the outermost layer of the skin (Figure 1), consists of dead keratinocytes (corneocytes) and constitutes a formidable physical barrier to delivery of vaccine components to immunologically rich skin layers (viable epidermis and dermis, Figure 1), thereby necessitating sophisticated skin-targeted drug delivery strategies for effective intracutaneous immunization [72][73][74]. Topical drug delivery is an appealing method for patients due to its simplicity and non-invasiveness; however, topical administration of antigenic compounds and biological adjuvants, which are relatively complex biomolecules, is hampered by the formidable barrier function of the superficial cutaneous layers, which substantially reduces the bioavailability of vaccines, and in turn, the efficacy of immunization [75][76][77].…”

Recent Advances of Microneedles and Their Application in Disease Treatment

“…On the basis of the previous studies, it can be seen that the functional design of MN drug delivery systems using nano-engineering technology could make it possible to realize intelligent control of drug release amount, release kinetics, or stimuli-responsive delivery. The main advantage of nanomaterials is that they can be designed for specific functions, and are responsive to specific microenvironments [ 5 ]. There are special microenvironments and landmark substances at the lesion site that could be extensively harnessed for the design of functional nanomaterials incorporating MNs for different diseases therapy.…”

“…The skin is the largest organ, and is a strong biological barrier, preventing infectious diseases and harmful substances from entering the body. However, the skin is also a major barrier to the effective delivery of drugs to lesions via percutaneous administration, while meanwhile also being susceptible to pain [ 5 ]. The skin consists of three morphologically distinct layers: the cuticle, the living epidermis, and the dermis [ 6 ].…”

Engineering Micro–Nanomaterials for Biomedical Translation

“…[ 19 ] Other applications include the delivery of pharmaceuticals for the treatment of cancer, skin conditions, bacterial infections, and osteoporosis. [ 20 ] Microneedles have also been applied for local anesthesia, pain management, and contraceptive purposes. More recently, microneedles have been used to sample skin fluids for diagnosis and health monitoring.…”