Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 635

commonly range from 100 to 1000 m in length are designed to pierce the SC, and
provide a direct and controlled route of access to the underlying tissue layers. When
inserted into the skin, microneedles create microscopic punctures through the SC and
into the viable epidermis. The length of the microneedle is controlled to ensure that
the depth of penetration does not encroach on the nerve fibers and blood vessels that
reside primarily in the dermal layer. The micron-sized channels therefore facilitate
the delivery of both small- and large-molecular-weight therapeutics into skin without
causing pain [82] and bleeding at the site of application.
Microneedles are used to augment the impact of concomitant delivery meth-
ods such as transdermal patches. Use of microneedles is a robust delivery for any
formulation—solution, suspension, emulsion, dry powder, and gel. This method
exposes large surface areas of the epidermis to the delivery agents rapidly (micronee-
dle arrays can contain over 1000 microneedles) and controls direct delivery of the
medicament. It does not need extra effort and is a convenient and painless delivery
for the patient. It is a minimally invasive methodology and suited to patient self-
administration, without the need for medical supervision. The materials, types of
structure, and dimensions of the needle can be adapted to facilitate the delivery of
macromolecules, nanoparticles, and vaccines [83] .
Solid microneedle arrays present an opportunity to create conduits through the
restrictive skin barrier layer. The formulation is applied into the channels, through
dry coating of the microneedle array or solution, suspension, emulsion, or gel con-
taining the medicament. The formulation is administered simultaneously and relies
on passive delivery mechanisms. The capacity to fabricate small hollow micronee-
dles allows a controlled quantity of the medicament to be actively delivered from the
tip of the inserted microneedle at a predefined rate and also provides the opportunity
to withdraw material from the skin for analysis and monitoring of response.
12.1.4.1.3 Phonophoresis/Sonophoresis
The use of ultrasound to enhance percutaneous absorption of a drug molecule is
called sonophoresis or phonophoresis [84-87] . The proposed mechanisms that
enhance skin penetration include cavitation, thermal effects, and mechanical per-
turbation of the SC [84,88] . It can be inferred that ultrasound acts on the barrier
function of the membrane. Sonophoresis has employed three distinct categories of
ultrasound:
1. High-frequency, or diagnostic, ultrasound (2-10 MHz)
2. Mid-frequency, or therapeutic, ultrasound (0.7-3 MHz)
3. Low-frequency ultrasound (5-100 kHz).
Ultrasound is defined as sound with a frequency longer than 16 kHz, although a
frequency of about 1 MHz is often used for diagnostic purpose. To attain biologic
effects from ultrasound, the energy must be captivated by the tissues. The depth of
penetration in tissue is controlled by the attenuation of sound, which is inversely
related to frequency. A contact medium or coupling agent is required to transfer
ultrasonic energy from the ultrasonic device to the skin and ultimately to the body.
A gel, emulsion, or ointment is used for purpose. The coupling agent may also be