Often associated with chemotherapy are the dangerous and sometimes lifethreatening
side effects towards non-cancerous tissue that can occur while on such drug
regimens. The design and utilization of macromolecular drug delivery vehicles is
gaining much attention because the vascular system of tumor tissue possesses properties
that make it permeable to macromolecules. The attachment or encapsulation of
anticancer drugs to macromolecules can be used to selectively deliver these drugs to
tumor tissue thereby minimizing the toxic effects towards healthy tissue while
specifically targeting the tumor. Moreover, the association of poorly water soluble drugs
with soluble macromolecules can increase the water solubility of such hydrophobic
drugs. Finally, association of chemotherapeutic agents with macromolecules can also
increase the drugs?? circulation time by decreasing the rate of renal clearance thus leading
to improve pharmacokinetics.
A class of spherical, hyperbranched polymers known as dendrimers has received
much attention as potential vehicles for anticancer drug delivery. Dendrimers based on
melamine might afford such use as macromolecular carriers for drug delivery. Therefore
an evaluation of melamine dendrimers is reported. The goal of objective one was to
assess both the in vitro and in vivo biocompatibilities of a cationic dendrimer based on
melamine. The results reported herein indicate that this particular species of dendrimer is
not suitable for in vivo use and did not warrant further investigation.
The goals of objective two were to see what impact surface modification had on
the in vitro and in vivo toxicities of a melamine dendrimer. The results presented here
indicate that surface modification of a cationic dendrimer to anionic or neutral species
can extensively increase biocompatibility. Moreover, the introduction of neutral
poly(ethylene glycol) (PEG) grafts affords the most protection in vitro and in vivo.
Interaction with albumin, controlled drug release, cellular uptake along with
favorable biodistribution patterns are vital factors that must be evaluated when screening
a drug delivery system. Evaluating the PEGylated dendrimer as a vehicle for anticancer
drug delivery, the goal of objective three, provides initial evidence that the PEGylated
dendrimer displays favorable characteristics as a vehicle for drug delivery and justifies
additional studies utilizing in vivo models.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/2401 |
| Date | 29 August 2005 |
| Creators | Neerman, Michael Frederick |
| Contributors | Simanek, Eric E. |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | 1749310 bytes, electronic, application/pdf, born digital |
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