Interactions of small polypeptides with dimyristoylphosphatidylcholine monolayers: effect of size and hydrophobicity

The effects of size and hydrophobicity of small (molecular weights below 2,000) polypeptides on their predominantly hydrophobic interactions with a neutral phospholipid monolayer were studied. The changes in surface pressure were determined when various concentrations of Gly, Gly-Gly-Gly, -Ala, -Ala- -Ala- -Ala, -Ala-Gly-Gly-Gly-Gly, -Phe- -Leu- -Glu- -Glu- -Leu, adrenocorticotropic hormone fragments 1–10 (ACTH-(1–10)), porcine β-lipotropin, -endorphin and human fibrinopeptide A were injected under dimyristoylphosphatidylcholine (DMPC) monolayers at an initial surface pressure of 10 dyne/cm. In all cases, when peptides with the same number of residues are compared, the concentration needed to increase the surface pressure of the film by 1 dyne/cm was inversely related to its hydrophobicity. A reasonably good correlation was found to exist between the calculated free energy of transfer of a polypeptide from ethanol to water (a measure of its hydrophobicity) and its ability to increase the surface pressure of the DMPC film (a measure of the extent of its interaction with the neutral lipid monolayer).     

Evaluation of the Interaction and Drug Release from α,β-Polyaspartamide Derivatives to a Biomembrane Model

This Article reports on a comparative study on the ability of various polymers, containing hydrophilic and/or hydrophobic groups, to interact with a biomembrane model using the differential scanning calorimetry (DSC) technique. Multilamellar vesicles of mixed dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidic acid (DMPA) were chosen as a model of cell membranes. The investigated samples were a water soluble polymer, the α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) and its derivatives partially functionalized with polyethylene glycol (PEG₂₀₀₀) to obtain PHEA-PEG₂₀₀₀, with hexadecylamine (C₁₆) to obtain PHEA-C₁₆, and with both compounds to obtain PHEA-PEG₂₀₀₀-C₁₆. These polymers are potential candidates to prepare drug delivery systems. In particular, some samples give rise to polymeric micelles able to entrap hydrophobic drugs in an aqueous medium. The migration of drug molecules from these micelles to DMPC/DMPA vesicles also has been evaluated by DSC analysis, by using ketoprofen as a model drug.     

Use of liposomes as carriers for immunomodulatory polypeptides: Studies on thymostimulin encapsulation and retention

The incorporation of thymostimulin, an immunoactive hormone extracted from calf thymus, into liposomes was characterized by means of DSC analysis. Changes in vesicle composition, as well as in the presence of cholesterol, led to variations in thermotropic behaviour and influenced their incorporation efficiency and stability. Among the prepared formulations, liposomes prepared using equimolar amounts of DPPC and DMPC showed the highest value (80%) for drug incorporation.     

Synergistic absorption enhancement of salmon calcitonin and reversible mucosal injury by applying a mucolytic agent and a non-ionic surfactant

Using high sensitivity differential scanning calorimetry (HSDSC), the phase transitions of dimyristoylphosphatidylcholine (DMPC) liposomal bilayers and their interaction with the model steroid beclometasone dipropionate (BDP) were found to be dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no phospholipid pretransition, a main transition of high enthalpy and a low onset temperature, and a very low incorporation of the steroid (maximum 1 mol%). This was attributed to an alcohol-induced interdigitation of the bilayers, which was not apparently reversed by flushing the liposome dispersion with nitrogen in an attempt to remove ethanol. For liposomes manufactured by thin film or particulate-based proliposome methods, 1–2.5 mol% steroid was optimal for incorporation within bilayers, although the nature of the steroid interaction with the bilayers differed between the two methods. For liposomes manufactured by the thin film method, a higher steroid concentration resulted in a broadened main transition and a reduced melting cooperativity. This suggests that BDP formed separate domains within the bilayers which caused non-ideal mixing and phase separation at 5 mol% steroid. This observation was absent for liposomes generated from particulate-based proliposomes, indicating separate steroid domains were not formed and subsequent non-ideal mixing and phase separation did not occur. In addition, liposomes generated from particulate-based proliposomes showed reduced pretransition and main transition enthalpies. These differences were attributed to the employment of sucrose to manufacture the particulate-based proliposomes. This study has shown that the thermal behaviour of liposomes and their interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Moreover, particulate-based proliposomes may provide a reasonable alternative to the conventional thin film method in producing liposomes incorporating this steroid.