**8. Conclusions**

Transdermal drug delivery has several potential advantages over other parenteral delivery methods. Apart from the convenience and noninvasiveness, the skin also provides a "reservoir" that sustains delivery over a period of days. Furthermore, it offers multiple sites to avoid local irritation and toxicity, yet it can also offer the option to concentrate drugs at local areas to avoid undesirable systemic effects. However, at present, the clinical use of transdermal delivery is limited by the fact that very few drugs can be delivered transdermally at a viable rate. This difficulty is because the skin forms an efficient barrier for most molecules, and few noninvasive methods are known to significantly enhance the penetration of this barrier.

In order to increase the range of drugs available for transdermal delivery the use of chemical and physical enhancement techniques have been developed in an attempt to compromise skin barrier function in a reversible manner without concomitant skin irritation. Recently, several alternative physical methods have emerged to transiently break the stratum corneum barrier and also the use of chemical enhancers continues expanding. The projectile methods use propelled microparticles and nanoparticles to penetrate the skin barrier. Microneedle arrays are inserted through the skin to create pores. "Microporation" creates arrays of pores in the skin by heat and radio frequency ablation. Also, ultrasound has been employed to disrupt the skin barrier. All these methods have their own advantages

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#### **9. Acknowledgments**

José Juan Escobar-Chávez wishes to acknowledge PAPIIT TA 200312 y PAPIIT IN 209709-3. The authors report no conflict of interests.

#### **10. References**


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**20** 

*Japan* 

**Application of Matrix-Assisted** 

**Mass Spectrometry** 

*Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University* 

Nobuhiro Zaima

**Laser Desorption/Ionization Imaging** 

The clarification of metabolic dynamics in lesion areas is important. Many approaches, such as high performance liquid chromatography mass spectrometry, gas chromatography mass spectrometry, immunohistochemistry, are used to define disease-related abnormalities. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is attracting attention as a new valuable tool. MALDI-IMS is a two-dimensional MALDI mass spectrometric technique used to visualize the spatial distribution of molecules without extraction, purification, separation, or labeling of biological samples (Cornett et al., 2007; Zaima et al., 2010b). MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins (Caprioli et al., 1997; Groseclose et al., 2007; Morita et al., 2010), peptides (Chansela et al., 2011; Stoeckli et al., 2002), amino acids (Goto-Inoue et al., 2010b; Zaima et al., 2010a), lipids (Hayasaka et al., 2009; Murphy et al., 2009; Zaima et al., 2011a), and carbohydrates (Goto-Inoue et al., 2010b), in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields, such as pharmacology, medicine, agriculture, biology, and pathology. In this review, we describe the methodology and

MALDI-MS was developed from laser desorption/ionization mass spectrometry (LDI-MS). The first LDI-MS experiment for high-mass molecules was reported in 1987 (Tanaka et al., 1987). In this experiment, a powder of cobalt metal in glycerol was used for the observation of ions with a mass to charge (*m/z*) ratio of 34,000. Soon afterward, MALDI-MS results of serum albumin (67,000 Da) were reported using nicotinic acid as the matrix (Karas & Hillenkamp, 1988). It was reported that MALDI-MS can detect a wide range of molecules ranging from small (*m/z* <1000) to large molecules (*m/z* >1,000,000) (Yates, 1998). The schema

In routine MALDI-MS analysis (i.e., non-imaging analysis), the analyte can be mixed with an excess of matrix. On the other hand, molecular imaging of tissue sections using MALDI-IMS requires the tissue surface to be homogeneously covered by a matrix. On-tissue

**1. Introduction** 

**2. MALDI-MS** 

applications of MALDI-IMS for biological samples.

of MALDI-MS is shown in Figure 1.
