Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?

Abstract

Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.

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].…”

Nanoemulsion Stabilized by Safe Surfactin from Bacillus subtilis as a Multifunctional, Custom-Designed Smart Delivery System

“…The stratum corneum consists of a series of layers of specialized skin cells that are continuously shedding, the role of which is to protect the inner layers of the skin [57]. Most of the chemical substances topically applied to the skin are not able to penetrate the stratum corneum [58]. Skin An analysis of the EPR spectra results presented in Figure 4 indicated a non-linear relationship between the DPPH• concentration and time.…”

“…The stratum corneum consists of a series of layers of specialized skin cells that are continuously shedding, the role of which is to protect the inner layers of the skin [57]. Most of the chemical substances topically applied to the skin are not able to penetrate the stratum corneum [58]. Skin penetration enhancement can be achieved chemically, physically or through the use of appropriate formulations [5], hence leading to the conclusion that nanoemulsions more effectively deliver active ingredients deep into the skin, making the formulation more effective.…”

<p>The Challenge of Nanovesicles for Selective Topical Delivery for Acne Treatment: Enhancing Absorption Whilst Avoiding Toxicity</p>

“…The stratum corneum represents the main skin barrier, and it reduces the efficacy of the topical treatment of different diseases, hindering drug permeation through the skin. 17 Over the past decade, nanomedicine and particularly topical drug delivery systems have been the focus of interest of different research groups because of their ability to overcome the limits of the skin barrier without altering the physiological and functional features. Moreover, they provide good therapeutic efficacy of the carried drug, increasing its local efficacy and also minimizing its side effects.…”