Nanoparticles to Cross Biological Barriers - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 96

molecules. Electroporation is a method in which a sequence of electrical
pulses can be used to disrupt the lipid structures in the skin. This has been
shown to create microscopic pores within the disrupted stratum corneum,
thus allowing the transport of drugs such as methotrexate through the skin
[116]. Microneedles, fabricated from metal, silicon, or polymer [117-119], have
been used to create a relatively painless mechanism for penetrating the skin
and delivering therapeutics. An advantage of using these microneedles is
that with a smaller needle comes less compression on the tissue as the needle
is inserted. This decreased compression can lead to less stimulation of pain
receptors as well as a decrease in discomfort associated with the insertion of
a larger-diameter needles.
Chemicals enhancers and bio-molecules are another means of increas-
ing the permeability of the skin [120, 121]. Chemical enhancers work by
partially solubilizing the lipid structure of the stratum corneum and have
been investigated via high-throughput methods developed by Mitragotri
et al. [120, 122]. Chemical enhancers make up a broad spectrum of chemi-
cal compounds, such as surfactants and fatty acids. These formulations
can include single-component systems, for instance ethanol [121], or multi-
component systems, such as sodium laureth sulfate with phenyl piperazine.
Aside from chemical enhancers, biochemical methods to penetrate the skin
have been investigated. Chen et al. [123] used a short, synthetic peptide to
increase the transdermal delivery of insulin in vivo. It appears the peptide
TD-1 (ACSSSPSKHCG) creates a temporary inlet by which insulin is able
to penetrate. Time-lapse studies of insulin blood concentration after topi-
cal administration following TD-1 treatment showed a marked decline after
15 minutes. These results suggest that while coadministration of TD-1 with
insulin was not requisite for improved transdermal delivery, the effects of
TD-1 were limited over time. Further investigation revealed that the peptide
increased FITC-labeled insulin concentrations deep within hair follicles, a
region populated with vasculature. The connection between hair follicle pen-
etration and improved systemic delivery has not been completely substanti-
ated. Magainin is a natural peptide that has also been shown to increase skin
permeability by disrupting the lipid structure within the stratum corneum
[124]. This peptide has previously been reported to increase the permeabil-
ity of bacterial membranes [125] by tightly binding lipids, creating a tension
that forms pores. When used in conjunction with the chemical enhancer
N-lauroyl sarcosine in an ethanol solution, magainin enhanced transdermal
permeability [124]. While these methods offer a means to increase skin per-
meability, nanoparticle formulations may offer a vehicle for the transdermal
delivery of drugs. Nanoparticle drug delivery systems could have an impact
on the delivery of large molecules or non-lipophilic drugs that are not as
viable for transcutaneous delivery.
Nanoparticles serve as vehicles for delivering a wide range of drugs, and
physico-chemical properties, including size, surface charge, and physical
morphology of nanoparticles, can be controlled for optimal transdermal