Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and microporous membrane transport, part 2: diffusion studies.

摘要: Peptide drugs are hydrophilic in nature and so their preferred pathway of membrane transport is by the paracellular route, which primarily involves passive diffusion across intercellular pores. The objective present study was to investigate effect secondary structure on aqueous a model polypeptide, poly(L-lysine), through microporous membrane. primary aim systematically evaluate variables (e.g. viscosity and/or hydrodynamic radius) that may contribute difference, if any, calculated values coefficient (D(aq)) for each conformer poly(L-lysine). Variations pH temperature medium were used induce structural changes Transport studies conducted 3 h at 25 or 37 degrees C using side-by-side cells. Hydrophilic polyester membranes with 1-microm pore diameter measure free conformer. apparent permeability (P(app)) D(aq) standard equations. solution determined radius then estimated. At C, both P(app) alpha-helix approximately same as those random coil In contrast, beta-sheet significantly (P < 0.05) less than solutions containing either the-helix conformers had viscosity. On other hand, higher when this absent. appeared have comparable sizes, whereas estimated larger two conformers. summary, changing poly(L-lysine) from did not affect its intrinsic D(aq). appearance decreased differences result well extended associated This strategy represent potential mechanism sustain delivery therapeutic peptide controlled drug device.