The diffusion coefficient (D) of peptide and protein drugs needs to be determined to examine the permeability through biological barriers and to optimize delivery systems. In this study, the D values of fluorescein isothiocyanate (FITC)-labelled dextrans (FDs) and peptides were determined and the permeability through a porous membrane was discussed. The observed D values of FDs and peptides, except in the case of insulin, were similar to those calculated based on a relationship previously reported between the molecular weight and D of lower-molecular-weight compounds, although the molecular weight range was completely different. The observed D value of insulin was between the calculated values for the insulin monomer and hexamer. The permeability of poly-lysine and insulin through the membrane was determined and the observed values were compared with predicted values by using the relationship between molecular weight and D and an equation based on the Renkin function. The observed permeability of insulin through the membrane was between that of the predicted permeability for the insulin monomer and hexamer. For the permeation of insulin, the determination of D was useful for estimating the permeability because of the irregular relationship between molecular weight and D. The methodology used in this study will be useful for a more quantitative evaluation of the absorption of peptide and protein drugs applied to mucous membranes.
We report the coupling of phase separation on a phospholipid membrane with a structural transition of giant DNA. We performed single-DNA measurements in the presence of cell-sized giant unilamellar vesicles (GUV) composed of dioleoylphosphatidylcholine (DOPC), phosphatidylethanolamine (PE), and cholesterol. We observed the effect of phase separation of the membrane by changing PE from dioleoylphosphatidylethanolamine (DOPE) to dipalmitoylethanolamine (DPPE), which corresponds to a change from a homogeneous single phase to two segregated phases of liquid-ordered and liquid-disordered states on the membrane. In the homogeneous membrane, DNA molecules exhibited a compact conformation in aqueous solution containing a physiological concentration of Mg2+ and polyamine, without attaching to the membrane surface. In contrast, in the membrane that was segregated into two domains, DNA molecules were adsorbed onto the liquid-ordered phase that was rich in DPPE by taking an elongated conformation.
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