Pharmaceutical Nanotechnology
In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery

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Abstract

Cell-based and acute and subchronic in vivo toxicity profiles of a dendrimer based on melamine reveal that this class of molecules warrants additional study as vehicles for drug delivery. In cell culture, a substantial decrease in viability was observed at 0.1 mg/mL. For the acute studies, mice were administered 2.5, 10, 40 and 160 mg/kg of dendrimer via i.p. injection. At 160 mg/kg, 100% mortality was seen 6–12 h after injection. For the other cohorts, blood chemistry work revealed no renal damage was taking place at 48 h. Liver enzyme activity nearly doubled for the mice treated at 40 mg/kg suggesting hepatotoxicity. For the subchronic studies, three i.p. injections of 2.5–40 mg/kg of dendrimers were administered at 3-week intervals. No mortality was observed. Forty-eight hours following the last administration, blood chemistry revealed no renal damage, but liver damage was indicated by elevated serum enzyme activity at the highest dose. Histopathological data further confirms that doses up to 10 mg/kg show no hepatic damage at subchronic doses. However, subchronic doses at 40 mg/kg lead to extensive liver necrosis.

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The note

The monodisperse, multivalent and globular nature of dendrimers has led many groups to consider their use as vehicles for drug delivery (Cloninger, 2002, Esfand and Tomalia, 2001, Patri et al., 2002, Aulenta et al., 2003). This use requires these architectures to display low toxicity and be biocompatible, nonimmunogenic, and biodegradable or subject to ready clearance. These studies address the acute and subchronic toxicity of molecule 1, a third generation, cationic dendrimer based on melamine

Acknowledgements

The National Institutes of Health (GM 64650) and the Center for Microencapsulation and Drug Delivery at Texas A&M University supported these investigations.

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Supplementary data associated with this article can be found at doi: 10.1016/j.ijpharm.2004.04.023.

1

Co-corresponding author. Tel.: +1-979-458-1538; fax: +1-979-845-0699.

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