Biomedical subjects

Alexander T Florence

Publications and source records attributed to Alexander T Florence.

21 records · Page 2Linked to original sources

PubMed2003

The interaction of cationic dendrons with albumin and their diffusion through cellulose membranes.

Amphipathic dendrons (partial dendrimers) having three lipidic (C(14)) chains coupled to dendritic lysine head groups with 8, 16 or 32 free terminal amino groups have been synthesised by solid phase peptide synthesis. Their interaction with albumin was studied in the presence of NaCl using dynamic dialysis, the diffusion of the dendrons through regenerated cellulose membranes also being studied. The stoichiometry of dendron: albumin interactions was found to be 1:1.5, 1:4 and 1:5 for the dendrons with 8, 16 and 32 amino groups, respectively. Membrane permeability P, membrane diffusion coefficient D and the membrane partition coefficient K values were calculated for each dendron. P and D values were low but highest for the 8 amino group dendron. The membrane partition coefficient K was greatest for the 8 amino group dendron. This was also the case with octanol/water partition coefficient studies. Considerable adsorption of the dendrons to the cellulose membrane occurred but NaCl decreased adsorption and improved diffusion of the dendrons through the cellulose membrane.

Adsorption↗

PubMed2003

Effect of physiological media on the stability of surface-adsorbed DNA-dendron-gold nanoparticles.

Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel cationic dendrons. The behaviour of this DNA-dendron-gold system in cell culture media has been described. Adsorption onto the gold nanoparticles of lipophilic cationic dendrons, with either 8 [(C12)(3)Lys7(NH2)(8)] or 16 [(C12)(3)Lys15(NH2)(16)] free amino groups on their outer surfaces and incorporating a nuclear localization signal peptide (NLS), resulted in positively charged nanoparticles with a corresponding small increase in particle size. Evidence suggested that the interaction between the gold nanoparticles and the dendron was mediated by hydrophobic forces. With an increase in ionic strength, the apparent particle size of the dendron-stabilized-gold particles increased, but at higher salt concentrations than plain gold sols. Addition of plasmid DNA did not markedly reduce the surface potential of the dendron-gold complex but resulted in an approximately 10-20% increase in hydro-dynamic diameter. Increasing ionic strength increased the apparent size of the DNA-dendron-gold particles, up to a maximum diameter of approximately 900 nm. Importantly, in cell culture media the size of the DNA-dendron-gold nanoparticles increased markedly, as surface potential was reduced. The presence of serum components partially ameliorated these effects, possibly due to steric stabilization of the particles. Release of the DNA from the complex was compromised in cell culture media (compared with water). This, coupled with the flocculation of the carrier, demonstrated the importance of testing delivery systems in the presence of relevant physiologically based fluids before cell culture or in-vivo studies.

Adsorption↗

PubMed2002

Loading into and electro-stimulated release of peptides and proteins from chondroitin 4-sulphate hydrogels.

Chondroitin 4-sulphate (CS) hydrogels were examined as potential matrices for the electro-controlled delivery of peptides and proteins. A CS hydrogel, cross-linked with ethylene glycol diglycidyl ether, and with a swelling ratio of 20, was used to study the influence of molecular size and shape of guest molecules on loading and release rates. Three positively charged molecules of different molecular weights (vasopressin MW 1084, aprotinin MW 6512 and lysozyme MW 14,400), and one negatively charged protein (bovine serum albumin MW 67,000) were used as model solutes. The hydrogels were loaded by equilibrium swelling. As a result, the three positively charged peptide and proteins were found to be concentrated in the gels, most likely due to ionic attraction between the negative charges in the gel polymeric backbone and the positively charged solutes. No such concentration of solute in the gel was seen for the negatively charged albumin. The latter is presumably loaded passively by diffusing in the water phase of the gel. The loading efficiency (indicated by the loading rate and the total amount of solute loaded in the gel) was found to increase with decreasing molecular size of solute. Electro-stimulated release of the loaded peptide and proteins was followed for 3 h during which an electric field was applied in pulses of 5 V (pulse duration and pulse interval were both of 20 min). The release of lysozyme and aprotinin from CS hydrogels responded to electrical pulses. On the other hand, vasopressin and albumin were largely released by passive diffusion and their release could not be electrically controlled. This work shows that the size of the guest molecule is an important parameter when electrically-stimulated drug release is desired, but further work obviously needs to be carried out with a larger range of molecular weights and conformations.

Aprotinin↗