A number of physical methods for drug penetration enhancement and improve bioavailability of the stratum corneum (SC) such as micro-needles, heating, iontophoresis, electroporation, and ultrasound have also been evaluated in the last decade. On the other hand, nanotechnology has shown remarkable potential in targetspecific delivery of drugs in the body. In this chapter, we discuss the role of overview about nanocarrier systems, physical enhancers and their possible combination in order to improve the passage of molecules through the organ systems. All these methods have their own advantages and disadvantages, nevertheless, novel developments are projected to be more adaptable to different needs.

Transdermal administration offers an interesting alternative to oral and parenteral drug administration; nevertheless, skin is an important barrier for drug absorption. Iontophoresis, a technique that consist of the application of low current density across a membrane can facilitate drug entrance through it. Iontophoresis can be used for local effects on skin, nail, eye or ear and it can also be used for systemic delivery when applied through skin. In this chapter, the mechanisms involved in drug transport during iontophoresis application and factors affecting its efficacy are reviewed. Examples of the use of iontophoresis in different fields are presented together with the most recent research.

Recent technological advances have re-established the value of DNA-based vaccines in tackling unmet medical needs. Such advances include the optimization of DNA plasmid constructs, the addition of novel molecular adjuvants into the formulations, and the development of in vivo delivery strategies such as electroporation (EP). The combination of DNA-based vaccines with the delivery platform of EP has enhanced the antigen expression by up to 1000-fold higher than DNA injection alone, resulting in greatly enhanced immunogenicity of DNA-based vaccines. Pre-clinical EPenhanced DNA-based vaccination has elicited robust functional host immune responses to a myriad of disease targets resulting in protection from viral challenge or tumor growth, depending on the disease model. Significantly, the problems encountered in translating these responses to the clinic have been overcome, and equally impressive immune responses are being observed in human beings when DNA-based vaccination is married with EP, as was observed in a recent clinical trial. In this review we will cover the principles of EP in respect to enhancing DNA-based vaccination protocols targeting pDNA delivery to the muscle or skin, and discuss the top line results that have revealed for the first time clinical efficacy of DNA-based vaccine candidates.

The administration of drugs in the skin using ultrasound is recognized like sonophoresis. The ultrasound is dating back to the fifties for high frequency (HF) and low frequency (LF). It has been investigated over the past two decades. Clearly, the use of ultrasound to drug delivery (DD) recently gained importance, thereby increasing patents and new commercial devices.

This chapter shows the important findings in sonophoresis. Particular attention is focused into therapeutical applications including transdermal drug delivery (TDD), gene therapy, sport medicine and sonophoretic devices.

This review provides a summary of studies on the use of radiofrequency to overcome the skin barrier in order to evaluate its therapeutic potential, primarily in the fields of drug delivery and gene therapy. Other applications in non-surgical dermatologic procedures, orthopedics and treatment of chronic pain are also addressed. Additionally, this chapter includes a description of common devices used in some of the fields described and information of risks, safety and cost of treatments in the area of medical skin procedures.

Transdermal drug delivery is a well-accepted route of administration for therapeutical drugs. Skin is the largest area human body organ, however, the substantial barrier property of the skin stratum corneum limits practical value of transdermal route of drug administration. It has been proved that microneedle array devices can overcome the barrier characteristics of the stratum corneum and enhance the delivery of therapeutic medicines through skin. This chapter focuses on looking at the microneedle-mediated transdermal drug delivery for therapeutical applications. The definition of microneedles, enhancement mechanisms and devices in research or in the market are also depicted.

At present, nanotechnology has acquired great importance. One of the fields where nanotechnology has been used with great success is medicine. This has allowed the emergence of a branch of nanotechnology called nanomedicine. Nanomedicine has been used by all known routes of administration (oral, intravenous, transdermal, etc.). Topical/transdermal route is one of the most used routes to administer formulated drugs in nanocarrier systems (nanoparticles, liposomes, dendrimer, transfersomes, nanoemulsion, etc.) in combination with the use of physical enhancers (microneedles, iontophoresis, sonophoresis, etc.). This route has great potential to deliver drugs, but the stratum corneum, which is the most external layer of the skin, confers properties of permeability to this organ.

In order to modify the skin barrier properties and use the skin as a route to administer drugs into the body, some interesting strategies have been developed in last decades, such as the use of chemical and physical enhancers and even the combination of these enhancers with nanocarrier systems. For this reason, this chapter mainly emphasizes the applications of the 3 main physical enhancers (ultrasound, iontophoresis and microneedles) with nanocarriers for administering drugs by topical/transdermal routes, where they have been more widely used.