DRUG DELIVERY AND DEVELOPMENT:

Topical Vaccination: No More Needles

I'm probably not the only person in the world who hates getting a shot. I can't quite put my finger on it, but there's something about being harpooned by a needle that I find unappealing.

Scientists have recently worked towards addressing this issue with insulin-deficient diabetics, developing an insulin delivery device that reduces the need for multiple daily injections. The diabetic regulates insulin release within the body by drinking tonic water.

Perhaps more desirable is a simple, topical drug delivery method, i.e. one that can be rubbed onto the skin and absorbed. Ignoring my needle-phobia, this would have many advantages in resource-limited nations, where there often aren't enough trained medical personnel for routine care.

The challenges of needleless vaccination.

The problem with this needlesless vaccination approach is that many water-soluble proteins (under study as advanced drugs) don't penetrate through the skin. Proteins are usually large molecules, skin cells are packed tightly together, and water-soluble proteins can't readily penetrate water-repelling cell membranes, all of which hinder the success of a topical drug delivery protocol.

This means that, for delivery inside the patient, many protein-based drugs require a shot (harpooning) or complicated delivery vehicles. To date, these delivery vehicles have invariably been toxic, expensive, and/or partially destroy the function of the protein.

Scientists have previously reported polymer microparticles, silica nanoparticles, and carbon nanotubes as drug delivery vehicles. While all of these protocols have their place (especially the carbon nanotubes, which are specifically designed to combat late-stage cancer), none of these methods conclusively fulfills all three desired requirements of safety, low cost, and protein functional retention, without the use of needles.

Victor Yang (University of Michigan Ann Arbor, United States) and coworkers have worked towards topical, needleless vaccination, utilizing a protocol likely to meet the approval of the United States Food and Drug Administration. Many drugs meet the requirements for delivery through the skin,

One example is an anti-HIV drug that can be mass-produced from genetically-modified Nicotiana benthamiana plants. This research is complimentary to the 2007 report of a rice-based (edible) cholera vaccine specifically designed for resource-limited nations.

Needleless vaccination.

For delivery across the skin, Yang and coworkers affixed a cell-penetrating peptide to various water-soluble proteins. The peptide enables the protein to penetrate through the skin.

Furthermore, the peptide they used is approved by the United States Food and Drug Administration. This approach is therefore likely to receive rapid regulatory approval.

The chemical bond between the peptide and the protein is a disulfide bond, which is readily cleaved within cells. Therefore, the delivery vehicle readily dissociates from the protein once across the skin and in the cell, suggesting that the function of the protein will be retained.

The scientists found that the proteins lysozyme, ovalbumin, and bovine serum albumin could penetrate through the skin via this protocol. Furthermore, the proteins were functional afterwards.

Mice which were topically adminsitered one of these proteins developed antibodies specific to the protein. In other words, there was an immune response, the desired effect of a vaccine.

Specifically, 500 micrograms per milliliter of ovalbumin ellicited an immune response. This response induced by needleless vaccination was statistically equivalent to standard injection with ovalbumin.

More impressively, targeting to the female reproductive tract was roughly 10 times as effective as standard injection. This result emphasizes that their new needleless vaccination protocol can in some respects exceed the protective benefit imparted by injection.

Implications.

The needleless vaccination method of Yang and coworkers is nontoxic, cheap, and retains the function of the protein-based drug comprising the vaccine. This approach is likely to speed its way through regulatory hurdles and, assuming trials in humans are successful, will be of much use in resource-limited nations.

for more information:

Huang, Y., Park, Y. S., Moon, C., David, A. E., Chung, H. S., & Yang, V. C. (2010). Synthetic Skin-Permeable Proteins Enabling Needleless Immunization Angewandte Chemie International Edition DOI: 10.1002/anie.200906153





