Template synthesized chitosan nano test tubes for drug delivery applications
There is tremendous current interest in developing nanoscale drug delivery vehicles. Though intensive efforts have focused on developing spherical drug delivery vehicles, cylindrically shaped vehicles such as nanotubes offer many advantages. Typically, nanotubes can carry a larger inner payload than nanoparticles of the same diameter. Also, we can prepare nanotubes in templates whose geometries can be controlled, in turn allowing precise control over the length and diameter of the tubes. In addition, template synthesized nanotubes can be differentially functionalized on the inner and outer surfaces. Furthermore, templates that are closed on one end can be used to fabricate nano test tubes (closed on one end). The geometry of these nano test tubes allows them to be easily filled with a payload, the open end sealed with a nanoparticle to protect the payload from leaking out, and then the exterior of the tube can be functionalized with a targeting moiety.
In an effort to develop such a system, we explored the fabrication of chitosan nano test tubes. Defect-free, chitosan nano test tubes of uniform size were synthesized within the pores of a nanoporous alumina template membrane. While the nano test tubes remained within the template membrane, their inner cavities were filled with a model payload. The payload was then trapped inside the nano test tubes by sealing the open ends of the tubes with latex nanoparticle caps. For proof-of-principle studies, imine linkages were used to attach the caps to the nano test tubes. To create a self-disassembling system, disulfide chemistry was used to covalently cap the nano test tubes. Once removed from the template, the exterior of the nano test tubes were modified with a targeting moiety, allowing them to be targeted to pathological sites. We have also shown that the chitosan nano test tubes are biodegradable by two systems: enzymatic cleavage by lysozymes and disulfide cleavage of the crosslinker by reducing environments (glutathione) found within cells. Therefore, once the nano test tubes reach their target site and are taken into a cell, the tubes can be degraded and release their payload. This chitosan nano test tube delivery stystem shows great potential for applications in targeted drug delivery. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)
0542: Chemical engineering