Abstract
Water-soluble, commercially-available poly(amidoamine) (PAMAM) dendrimers are highly-branched, well-defined, monodisperse macromolecules having an ethylenediamine core and varying surface functional groups. Dendrimers are being employed in an increasing number of biomedical applications. In this study, commercially obtained generation 5 hydroxyl-terminated (G5OH) PAMAM dendrimers were studied as potential proteomimetics for ophthalmic uses. To this end, the surface of G5OH PAMAM dendrimers were hydrophobically modified with varying amounts of dodecyl moieties, (flexible long aliphatic chains), or cholesteryl moieties (rigid lipid found in abundance in biological systems). Dendrimers were characterized by 1H-NMR, DLS, DSC and HPLC. The hydrophobic modification caused aggregation and molecular interactions between dendrimers that is absent in unmodified dendrimers. In vitro tissue culture showed that increasing the amount of dodecyl modification gave a proportional increase in toxicity of the dendrimers, while with increasing cholesteryl modification there was no corresponding increase in toxicity. Storage and loss modulus were measured for selected formulations. The hydrophobic modification caused an increase in loss modulus, while the effect on storage modulus was more complex. Rheological properties of the dendrimer solutions were comparable to those of porcine lens crystallins.
Highlights
Since the biological properties of poly(amidoamine) dendrimers are tuned with variations of their terminal functionality, it is important to qualify the biocompatibility of any new classes of derivatives of PAMAM dendrimers proposed for biological applications
Amine or carboxyl terminated) dendrimers because of their potential uses in controlled drug or gene delivery, we selected G5OH PAMAM dendrimers to study the effect of hydrophobicity on their biological behaviors as they are more suited to our intended ophthalmic applications
Dendrimer with either dodecyl chloroformate or cholesteryl chloroformate
Summary
Water-soluble, commercially-available poly(amidoamine) (PAMAM) dendrimers are highly branched, well defined, monodisperse macromolecules having an ethylenediamine core and surface functional groups of one of three main types (primary amine, hydroxyl, or carboxylate termini) [1,2] These dendrimers are functionalized and have shown potential applications in nanomedicine such as drug carriers, gene delivery vectors, biosensors, imaging or contrast agents, cell labeling, bioartificial liver systems and tissue scaffolds [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. Since the biological properties of poly(amidoamine) dendrimers are tuned with variations of their terminal functionality, it is important to qualify the biocompatibility of any new classes of derivatives of PAMAM dendrimers proposed for biological applications
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