**3.4 Noble metal types**

Thermocouples employing platinum and platinum-rhodium alloys for their thermoelement (Noble-metal thermocouple types B, R and S) have been used for many years and exhibit a number of advantages over the base metal types. They are most resistant to oxidation, their thermoelements have higher melting points, and they have generally been found to be more reproducible at elevated temperatures in air. They are therefore used when higher accuracy and longer life is sought, though more experience with lower thermopowers.

Of all the standardized thermocouples, Type **S,** Platinum-10% rhodium (+) vs. Platinum (-) is the oldest and perhaps the most important. Type B, Platinum-30% rhodium (+) vs. Platinum-6% rhodium (-), was adopted as a standard type in the US in the late 1960s primarily to serve requirements in the 1200 to 1750oC range. At elevated temperatures, it offers superior mechanical strength and improved stability over types R and S, and it exhibits comparable thermopower. Its thermopower diminishes at lower temperatures and is vary small in the room-temperature range.

Identification of noble metal thermocouple wires is made difficult by the fact that all alloys are nearly identical in colour and all are non-magnetic. Sometimes it is possible to distinguish the positive wire from the negative one for types R or S by observing the 'limpness' of the wires. Pure platinum wires tend to be slightly more soft, or limp, while the rhodium-alloyed conductors are a little stiffer, enough so to permit identification. The differences, however, are subtle, and it is not possible to tell one rhodium alloy from another by these means. Proper connections for these thermocouples can be reliably determined by gently heating the junction and observing the resulting polarity on a sensitive indicator.


**About the Editors**

### **Guining Lu**

Guining Lu is a Professor at School of Environment and Energy, South China University of Technology, China. He received his Ph.D. degree in environmental engineering in 2008, jointly trained by South China University of Technology and Rutgers University. He focuses on soil/water pollution control and remediation technology, and the structure–activity relationship of environmental organic pollutants. He is interested in pollution control, soil remediation, e-waste, mining area, heavy metals, persistent organic pollutants, and polybrominated diphenyl ethers.

### **Zenghui Diao**

Zenghui Diao is a Professor at College of Resources and Environment, Zhongkai University of Agriculture and Engineering, China. He received his Ph.D. degree in environmental engineering from Sun Yat-sen University in 2013. He worked in Chinese Academy of Sciences, China four years from 2014 to 2018, and joined Zhongkai University of Agriculture and Engineering as a professor since June 2018. His research interests mainly focus on environmental remediation and plant protection, water treatment, and soil remediation.

### **Kaibo Huang**

Kaibo Huang is an Associate professor at School of Environment and Ecology, Hainan University, China. He received his Ph.D. degree in environmental science and engineering in 2021 jointly trained by South China University of Technology and Purdue University. He mainly focuses on environmental fate of contaminants, with a particular interest in tropical offshore. He has expertise in soil washing, photo-transformation, surfactant, e-waste, polychlorinated biphenyls, bi-metal, and emerging contaminants.


**3. Routes of drug penetration through the skin**

The permeation of drugs through the skin involves the diffusion through the intact epidermis through the skin appendages (hair follicles and sweat glands). These skin appendages form shunt pathways through the intact epidermis, occupying only 0.1% of the total human skin. It is known that drug permeation through the skin is usually limited by the stratum corneum (Fig. 2). Three main penetration routes are recognized (Fig. 3).

**Figure 1.** Structure of the skin (http://www.naturalrussia.com/natural/skin/structure.html. Downloaded on April 26, 2014)

(http://www.spring8.or.jp/en/news\_publications/press\_release/2011/110406/. Downloaded April 26, 2014).

**Figure 2.** The stratum corneum

Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. TDDS were introduced into the US market in the late 1970s [5], but trans‐ dermal delivery of drugs had been used for a very long time. There have been previous reports about the use of mustard plasters to alleviate chest congestion and belladonna plasters as analgesics. The mustard plasters were homemade as well as available commercially where mustard seeds were ground and mixed with water to form a paste, which was in turn used to form a dispersion type of delivery system. Several methods have been examined to increase the permeation of therapeutic molecules into and through the skin and one such approach is

The skin has been an important route for drug delivery when topical, regional, or systemic effects are desired. Nevertheless, skin constitutes an excellent barrier and presents difficulties for the transdermal delivery of therapeutic agents, since few drugs possess the characteristics required to permeate across the stratum corneum in sufficient quantities to reach a therapeutic concentration in the blood [6]. In order to enhance drug transdermal absorption, different methodologies have been investigated, developed, and patented. Improvement in physical permeation-enhancement technologies has led to renewed interest in transdermal drug delivery. Some of these novel advanced transdermal permeation-enhancement technologies include iontophoresis, electroporation, ultrasound, microneedles to open up the skin, and

The potential of using the intact skin as the port of drug administration to the human body has been recognized for several decades. However, the skin is a very difficult barrier to the ingress of materials allowing only small quantities of a drug to penetrate over a period of time. In order to design a drug delivery system, one must first understand the skin anatomy and its

of three main layers; the epidermis, dermis and hypodermis (subcutaneous layer) (Fig. 1). The skin is a well energized organ that protects the organism against environmental factors and

The permeation of drugs through the skin involves the diffusion through the intact epidermis through the skin appendages (hair follicles and sweat glands). These skin appendages form shunt pathways through the intact epidermis, occupying only 0.1% of the total human skin. It is known that drug permeation through the skin is usually limited by the stratum corneum

. It is composed

The human skin is the largest organ in our body with surface area of 1.8-2.0 m2

use of nanoparticulate delivery system.

194 Application of Nanotechnology in Drug Delivery

more recently the use of transdermal nanocarriers.

implication of drug-of choice and method of delivery.

**3. Routes of drug penetration through the skin**

(Fig. 2). Three main penetration routes are recognized (Fig. 3).

regulates heat and water loss from the body.

**2. The human skin**

#### **3.1. The intercellular lipid route**

Interlamellar regions in the stratum corneum, including linker regions, contain less ordered lipids and more flexible hydrophobic chains. This is the reason for the nonplanar spaces between crystalline lipid lamellae and their adjacent cells' outer membrane. Fluid lipids in skin barrier are crucially important for transepidermal diffusion of the lipidic and amphiphilic molecules, occupying those spaces for the insertion and migration through intercellular lipid layers of such molecules [7]. The hydrophilic molecules diffuse predominantly "laterally" along surfaces of the less abundant water-filled interlamellar spaces or through such volumes; polar molecules can also use the free space between a lamella and a corneocyte outer membrane to the same end.

#### **3.2. The transcellular route**

Intracellular macromolecular matrix within the stratum corneum abounds in keratin, which does not contribute directly to the skin diffusive barrier but supports mechanical stability and thus intactness of the stratum corneum. Transcellular diffusion is practically unimportant for transdermal drug transport [8]. The narrow aqueous transepidermal pathways have been observed using confocal laser scanning microscopy. Here, regions of poor cellular and intercellular lipid packing coincide with wrinkles on skin surface and are simultaneously the sites of lowest skin resistance to the transport of hydrophilic entities. This lowest-resistance pathway leads between clusters of corneocytes at the locations where such cellular groups show no lateral overlap. The contribution to transdermal drug transport can increase with pathway widening or multiplication, e.g., that which is caused by exposing the stratum corneum to a strong electrical (electroporation/iontophoresis), mechanical (sonoporation/ sonophoresis), or thermal stimulus, or suitable skin penetrants.

#### **3.3. Follicular penetration**

Recently, follicular penetration has become a major focus of interest due to the fact that drug targeting to the hair follicle is of great interest in the treatment of skin diseases. However, follicular orifices occupy only 0.1% of the total skin surface area. For this reason, it was assumed to be a nonimportant route for drug penetration. But a variety of studies have shown that hair follicles could be an interesting option for drug penetration through the skin [6]. Such follicular pathways have also been proposed for topical administration of polystyrene nanoparticles. They were investigated in porcine skin (*ex vivo*) and human skin (*in vivo*). Surface images revealed that polystyrene nanoparticles accumulated preferentially in the follicular openings. This distribution was increased in a time-dependent manner, and the follicular localization was favored by the smaller particle size. The study also confirmed similarity in the penetration between both membranes (porcine and human skin). In other investigations, the influence of microparticle size in skin penetration has been shown by differential stripping. Nanoparticles can act as efficient drug carriers through the follicle or can be utilized as follicle blockers to stop the penetration of topically applied substances.

in-process operations and conditions such as stirring rate, temperature, type and amount of dispersing agent as well as the viscosity of the organic and aqueous phases [9,10]. Zeta potential

**Figure 3.** Structure of the skin showing routes of penetration: (1) across the intact horny layer, (2) through the hair follicles with the associated sebaceaous glands, or (3) via the sweat glands (http://www.skin-care-

Nanoparticles for Dermal and Transdermal Drug Delivery

http://dx.doi.org/10.5772/58672

197

forum.basf.com/en/author-articles/strategies-for-skin-penetration-enhancement/2004/08/12? id=5b9a9164-6148-4d66-bd84-6df76bd6d111&mode=Detail. Downloaded April 26, 2014).

The attachment of nanoparticles to cell membrane is affected by the surface charge of the particles. Variation of the particle surface charge could potentially control binding to the tissue and direct nanoparticles to cellular compartments both *in vitro* and *in vivo*. Cellular surfaces are dominated by negatively charged sulphated proteoglycans molecules that play pivotal roles in cellular proliferation, migration and motility [12]. Cell surface proteoglyans consist of a core protein anchored to the membrane and linked to one or more glycosaminoglycan side chains (heparan, dermatan, keratan or chondrotine sulfates) to produce a structure that extends

of a dispersion is necessary for dispersion stability [11].

**4.2. Surface properties**

away from the cell surface.