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Interactions of PAMAM dendrimers with model lipid membranes
Author(s) -
Tiriveedhi Venkataswarup,
Kitchens Kelly M,
Ghandehari Hamid,
Butko Peter
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a981-c
Subject(s) - dendrimer , calcein , chemistry , dissociation constant , lipid bilayer , biophysics , membrane , vesicle , fluorescence anisotropy , bilayer , polymer chemistry , biochemistry , biology , receptor
Dendrimers and other cationic macromolecules in general are considered potential vehicles for intracellular drug delivery. We used fluorescence spectroscopy to study the interaction of cationic PAMAM (polyamidoamine) dendrimers with model lipid bilayers. When the dendrimers interacted with small unilamellar vesicles (SUV) loaded with the self‐quenching fluorophore calcein they did not induce release of calcein neither with neutral SUV (made of egg phosphatidylcholine) nor negatively charged SUV (with 25% egg phosphatidylglycerol). The G1 (generation 1, Mr = 1430) dendrimer was labeled with fluorescein and the G4 dendrimer (Mr = 14215) with a similar fluorophore Oregon green, and their membrane interactions were followed by changes in fluorescence anisotropy during titrations with lipid. The anisotropy changed linearly with the density of negative charge in the membrane. The addition of high salt caused redissociation of the dendrimers from SUV. These two observations prove the electrostatic nature of the interaction. Analysis of the binding data yielded values of the dissociation constants Kd. For G1‐dendrimer, Kd = 30 +/‐ 16 uM with neutral SUV and Kd = 11 +/‐ 3 M with negatively charged SUV. For G4, which carries much higher charge on its surface, exhibited lower dissociation constants, Kd = 16 +/‐ 7 uM with neutral SUV and 5 +/‐ 1 uM with negatively charged SUV. We conclude that the interaction of PAMAM dendrimers with lipid membrane is electrostatic and the dendrimer binding does not significantly disrupt the bilayer integrity.