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Alexandros Pantos

Publications and source records attributed to Alexandros Pantos.

4 recordsLinked to original sources

Interaction of functional dendrimers with multilamellar liposomes: design of a model system for studying drug delivery.

Multilamellar liposomes consisting of phosphatidylcholine-cholesterol-dihexadecyl phosphate (19:9.5:1 molar ratio) and dispersed in aqueous or phosphate buffer solutions were interacted with poly(propylene imine) dendrimers which were partially functionalized with guanidinium groups. The remaining toxic external primary amino groups of the dendrimers were reacted with propylene oxide, affording the corresponding hydroxylated derivatives. Microscopic, zeta-potential, and dynamic light scattering techniques have shown that liposomal-dendrimeric molecular recognition occurs due to the interaction between the complementary phosphate and guanidinium groups. Calcein liposomal entrapment experiments demonstrate a limited leakage, i.e., less than 13%, following liposomes interaction with the modified dendrimers. Calorimetric studies indicate that the enthalpy of the interaction is dependent on the number of guanidinium groups present at the dendrimeric surface and the medium. The process is reversible, and redispersion of the aggregates occurs by adding concentrated phosphate buffer. Two corticosteroid drugs, i.e., betamethasone dipropionate and betamethasone valerate, were encapsulated into the functionalized dendrimers. Drug transport from guanidinylated dendrimers to multilamellar liposomes ranges from 40% to 85%, and it is also dependent on the medium and the degree of dendrimer guanidinylation.

Cholesterol↗

Enhanced drug transport from unilamellar to multilamellar liposomes induced by molecular recognition of their lipid membranes.

Unilamellar PC-based liposomes bearing a recognizable moiety were loaded either with the hydrophilic drug doxorubicin (DXR) or with the hydrophobic drug tamoxiphen (TMX) and allowed to interact with multilamellar PC-based liposomes bearing complementary recognizable groups. It has been established that, due to molecular recognition of these complementary liposomes, effective and fast transport of the drugs occurs from unilamellar to multilamellar liposomes. The transport of TMX is more effective compared to that of DXR. This behavior was observed for both PEGylated and non-PEGylated unilamellar liposomes, and it was attributed to the different sites of solubilization of the drugs in the unilamellar liposomes. PEGylation reduces the transport of both drugs since it inhibits to some extent the molecular recognition effectiveness of the complementary moieties.

Liposomes↗

Interactions of complementary PEGylated liposomes and characterization of the resulting aggregates.

The interaction of complementary liposomes bearing both recognizable and protective ligands at their external surface has been investigated. Aggregation of hydrogenated phosphatidyl choline/cholesterol (2:1 molar ratio) based liposomes was mediated by the molecular recognition of the complementary phosphate and guanidinium groups incorporated in separate unilamellar liposomes. The phosphate group was incorporated in the bilayer employing dihexadecyl phosphate, while the guanidinium moiety was introduced in the membrane through the incorporation of various guanidinium lipids. For the latter, anchoring ability and primarily introduction of a spacer group between their lipophilic part and the guanidinium group was found to affect the ability for molecular recognition. Also, poly(ethylene glycol) (PEG) introduced in both types of liposomes at various concentrations and up to 15% with respect to cholesterol modifies the interaction effectiveness and morphology of the obtained aggregates. Interaction of these complementary liposomes leads to large precipitating aggregates or fused liposomes, as shown by phase contrast microscopy and dynamic light scattering. Specifically, fusion of liposomes takes place under a nonleaking process involving lipid mixing, as demonstrated by calcein entrapment and resonance energy transfer experiments. Calorimetric parameters also correlate with the processes of aggregation and fusion. The interactions of non-PEGylated liposomes involve exothermic processes of higher enthalpic content than those of the PEGylated counterparts.

Cholesterol↗

Complementary liposomes based on phosphatidylcholine: interaction effectiveness vs protective coating.

A prospective targeted drug delivery system was prepared by the introduction of complementary and protective moieties at the external surfaces of liposomes. Thus recognition between hydrogenated phosphatidylcholine-cholesterol-based liposomes was achieved by the interaction of the complementary phosphate and guanidinium groups incorporated in separate liposomes while polyethylene glycol chains (PEG) protected both liposomes from environmental factors. In general, protective coating of liposomes in the range of 5% molar incorporation exerted an inhibitory effect on their recognition but it also permitted effective interaction between complementary liposomes.

Cholesterol↗