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Hydrophobic Dendrimer-Derived Nanoparticles

Hydrophobic Dendrimer-Derived Nanoparticles

Baljit Singh, Alexander T Florence

Int J Pharm. 2005 Jul 25;298(2):348-53.

PMID: 15913929

Abstract:

Lipidic polylysine dendrimers, synthesized using Fmoc solid phase peptide techniques, have been formulated as nanoparticles by precipitation from solution in dichloromethane. The effect of concentration on the diameter and stability of nanoparticles formed from two short homologous series of dendrimers--one fifth generation and one sixth generation series and with surface C4, C10 or C12 groups--was investigated using photon correlation spectroscopy. The increase in generation from fifth to sixth resulted in increased diameter for each chain length. An increase in the surface lipidic chain length from C4 to C12 had no effect on the particle diameter of aggregates derived from fifth generation dendrimers, and a small and variable effect on the sixth generation derived nanoparticles. Using pyrene (excitation 340 nm) as a hydrophobic fluorescent probe, a decrease in intensity peak I1 (374 nm)/I3 (385 nm) in the emission spectra (340-600 nm) was observed in the two dendrimers studied, fifth generation dendrimers with C10 or C12 surface lipidic chains, as the dendrimer concentration increased, reaching a plateau at higher concentrations, indicating that a more compact form of the aggregates with a more hydrophobic interior was obtained. Apart from the hydrophobicity of the dendrimers and dendrimer concentration, the flexibility of the dendrimers might have a significant effect in determining nanoparticle size. The aggregates derived from the fifth generation dendrimers with C10 or C12 surface lipidic chains are stable in purified intestinal fluid but not in purified stomach fluid, in which further aggregation of the nanoparticulate dendrimer aggregates occurs as an effect of pH, salts, proteins and enzymes in these fluids. This study demonstrates, inter alia, the importance of testing nanoparticulate delivery systems in relevant physiologically based fluids prior to their use in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP204401843-A	PAMAM-25% C12 dendrimer, generation 2 solution		204401-84-3	Price

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