(181aa) Investigation of PVA Microneedle for Protein Delivery | AIChE

(181aa) Investigation of PVA Microneedle for Protein Delivery

Authors 

Aljewari, H. - Presenter, University of Arkansas
de Castro, R., University of Arkansas
Thompson, A., University of Arkansas

Investigation of PVA
Microneedle for Protein Delivery

The delivery of drugs containing proteins continues to be a
challenge. Topical creams are not suitable for delivery since proteins are not capable
of passively crossing the stratum corneum. Oral delivery although useful often
leads to some protein degradation before reaching the target site and using hypodermal
needles can be painful and pose a risk of contamination as well as waste
disposal issues. Microneedles are an attractive alternative to traditional dermal
drug delivery since they can be specifically designed to deliver proteins painless
and more effectively.

By using microneedles made of poly(vinyl alcohol) (PVA), we
provide a safer alternative with no disposal issues, while producing
microneedles that are less painful and capable of delivering the contents straight
to the stratum corneum, therefore avoiding protein degradation. PVA
has been used extensively used in microneedle production due to its
biocompatibility, non-toxic and non-carcinogenic nature, swelling properties
and bioadhesive characteristics [1]. PVA has been used in the delivery of
gentamicin and smaller proteins like insulin [2, 3]. However, the ability to
deliver larger proteins is still being developed. The potential for loading
larger molecules will greatly expand the use of microneedles for drug delivery,
especially in vaccine production. Therefore, we are currently working on the
fabrication of a PVA microneedle membrane capable of housing and delivering a
38kD protein, Pneumococcal
surface protein A (PspA). We hypothesize that the biodegradable quality of PVA
will aid the release of large proteins that may get stuck in the needles,
consequently increasing the concentration of protein being delivered.

We have
used the freeze-thaw method to create a PVA membrane to test the release of
three proteins; chicken egg white lysozyme (CEWL) of molecular weight of 14.4
kDa, chicken ovalbumin (OVA) 42.7 kDa, and Bovine Serum Albumin (BSA) of 66.5
kDa. Protein containing membranes were studied for
release and diffusion.
Our preliminary data showed the release of CEWL, the
smallest protein at 14kDa, after 24 hours. By extending
the freeze-thaw cycles, we were able to increase the amount of protein released

by 38% in comparison to the amount of protein diffused. This is
due to the size of the protein and the pore size. We also determined the polymer concentration does not play
a role in a release. The data suggests that our current method results in pores
that are more conducive to a smaller protein. We plan to further
investigate the membrane protein interaction to determine the membrane
structural changes as it relates to release, as well as the protein integrity
upon release.

In the future, we will be using a microneedle mold of 0.8mm
needle size to cast protein loaded PVA to test the protein release.

1.      
Larrañeta, Eneko, et al. “Microneedle Arrays as Transdermal and
Intradermal Drug Delivery Systems: Materials Science, Manufacture and
Commercial Development.” Materials Science and Engineering R: Reports,
vol. 104, 2016, pp. 1–32, doi:10.1016/j.mser.2016.03.001.

2.       González-Vázquez,
Patricia, et al. “Transdermal Delivery of Gentamicin Using Dissolving
Microneedle Arrays for Potential Treatment of Neonatal Sepsis.” Journal of
Controlled Release
, vol. 265, Elsevier B.V., Nov. 2017, pp. 30–40, doi:10.1016/j.jconrel.2017.07.032.

3.       Nejad,
Hojatollah Rezaei, et al. “Low-Cost and Cleanroom-Free Fabrication of
Microneedles.” Microsystems & Nanoengineering, vol. 4, Springer
Nature, Jan. 2018, p. 17073, doi:10.1038/micronano.2017.73.