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The evaluation of melamine dendrimers as potential macromolecular vehicles for anticancer drug delivery
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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.
Neerman, Michael Frederick (2006). The evaluation of melamine dendrimers as potential macromolecular vehicles for anticancer drug delivery. Doctoral dissertation, Texas A&M University. Texas A&M University. Available electronically from