Microneedling in Clinical Practice

Boris Stoeber, Raja K. Sivamani, Howard I Maibach, Boris Stoeber, Raja K. Sivamani, Howard Maibach, Howard I Maibach

• Publisher: CRC Press
• Year: 2020
• eBook ISBN: 9781351967693
• Edition: 1
• Topic: Medicine
• Subtopic: Dermatology

Microneedles provide an artificial pathway across the skin barrier for medical and cosmetic applications. This technology has seen a significant increase in popularity over the past years; as an example, the use of multiple small needles mounted on a roller to pierce the skin, prompting it to stimulate collagen production, has undergone a resurgence of interest as an adjunctive procedure for a number of skin disorders. This monograph draws together what is known about how to integrate microneedle technology into clinical dermatologic practice.

1

Microneedles and Transdermal Transport

Ashley Clark

University of Pennsylvania Perelman School of Medicine

Raja Sivamani

University of California-Davis

Pacific Skin Institute

1.1 Anatomy of the Skin

As the outermost layer of the body, the skin serves many roles including protection against UV radiation and microbes, regulating the movement of substances into and out of the body, and maintaining water and temperature equilibrium.¹ In order to perform its specialized functions, skin is divided into three layers: the epidermis, the dermis, and the hypodermis.

1.1.1 Stratum Corneum and Epidermis

The epidermis is the outermost layer of the skin and can range from 0.04 mm to 1.5 mm in thickness (Table 1.1), based on age, gender, ethnicity, and location on the body.² It is composed of self-regenerating stratified squamous epithelium, and serves as a protective barrier to the structures underneath. It is further separated into four layers: stratum corneum, stratum granulosum, stratum spinosum, and stratum germinativum. The stratum corneum consists of dead keratinocytes that form a relatively impermeable barrier to transdermal movement.

TABLE 1.1 Epidermal Thickness at Various Anatomical Sites

Body Site	Stratum Corneum (µm)	Mean Epidermal Thickness (µm)
Temple	6.3	61.4
Chest	6.5–12.8	56.0
Abdomen	6.3	61.3
Outer forearm	10.9–19.5	60.3
Leg	20.5–22.5	61.8
Dorsum of hand	9.3	84.5
Fingertip	160–209 (palm)	369.0

Adapted from Whitton et al.,³ Robertson et al.,⁴ and Bohlin et al.⁵

1.1.2 Dermis

The dermis is the layer of skin underlying the epidermis, measuring 1–2 mm in thickness.⁶ It consists of nerves, vasculature, hair follicles, and glandular structures, held in place by a network of elastin and collagen fibers embedded in ground substance, which is the gel-like extracellular matrix that exists in the extracellular spaces.

1.1.3 Hypodermis

The hypodermis, also called the subcutaneous layer, is composed of approximately 3 mm of loose, well-vascularized connective tissue, and serves as adhesion to the bone and muscle. It also provides additional cushion and insulation.⁶

1.2 Modes of Transdermal Delivery

The skin is an appealing target for drug delivery for several reasons. Drug delivery through the skin is often minimally invasive and allows for more frequent administration. It also provides a larger surface area for drug absorption. And finally, transdermal drug delivery bypasses hepatic first-pass metabolism and deactivation through gastric enzymes.⁷

Unfortunately, the skin's effectiveness as a barrier makes transdermal drug delivery a difficult task. The stratum corneum is the primary gatekeeper, preventing the movement of large, polar substances across the skin. For this reason, a certain amount of creativity is required to purposely bypass the stratum corneum and deliver drugs directly to the vascular dermis.

Multiple solutions have been attempted to assist in drug delivery across the skin by increasing the permeability of the stratum corneum. These typically fall into two categories: chemical and physical enhancers (Table 1.2).

1. Chemical enhancers: Chemical enhancers work by interacting with the lipid bilayer of the stratum corneum to reversibly compromise the skin barrier, and allow for the penetration of drugs that would normally have difficulty crossing the stratum corneum. Although they are minimally invasive, chemical enhancers can cause significant irritation.⁸ Listed below are various types of chemical enhancers.⁹
   1. Solvents (methanol, chloroform, acetone, pyrrolidones, sulphoxides)¹⁰
   2. Detergents
   3. Liposomes
   4. Nanoparticles
2. Physical Enhancers:⁸
   1. Iontophoresis: Iontophoresis involves the use of a small electrical current, either directly or indirectly, to aid in the movement of charged particles across the skin.
   2. Electroporation: Electroporation, unlike iontophoresis, uses high-voltage pulses to create small pathways within the skin's lipid bilayer, resulting in increased skin permeability.¹¹
   3. Sonophoresis: Like electroporation, high-frequency sonophoresis also forms small holes in the skin to increase drug permeability. However, sonophoresis relies on ultrasound waves. It has been used to deliver topical steroids and NSAIDs.¹²
   4. Microneedles: Microneedles form...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Contents
• Contributors
• Chapter 1 Microneedles and Transdermal Transport
• Chapter 2 Skin Perforation and Solid Microneedles
• Chapter 3 Dissolvable and Coated Microneedle Arrays: Design, Fabrication, Materials, and Administration Methods
• Chapter 4 Hollow Microneedles
• Chapter 5 Microneedles vs. Other Transdermal Technologies
• Chapter 6 Combination of Microneedles with Other Methods
• Chapter 7 Medical Applications of Microneedles
• Chapter 8 Therapeutic Drug and Biomolecule Monitoring Potential for Microneedle Technologies
• Chapter 9 Commercialized Microneedles
• Chapter 10 Considerations for Clinical Trials Involving Microneedle Devices
• Chapter 11 Microneedling in Clinical Practice: Cosmetic applications
• Chapter 12 Dermatotoxicology of Microneedles in Man
• Index