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Biophysical Model Drug-delivery System to Study sPLA2 Activity

Biophysical Model Drug-delivery System to Study SPLA2 Activity [Pg.47]

Permeability enhancers (lysolipid + fatty acid) Proenhancer (lipid) [Pg.47]

Effect of Lipid Composition on sPLA -triggered Drug Release and Absorption [Pg.48]

When SPLA2 is added to the liposome suspension, a slow release of calcein is observed from the target liposomes (Fig. 3.4). This period of slow release, which is clearly observed for the bare DPPC liposomes, corresponds to the well-known lag time of sPLA2- A pronounced decrease in the lag time and a concomitant enhancement of the release of calcein across the target membranes is observed when 2.5 mol% DPPE-PEG2000 is incorporated into the carrier liposomes. When short-chain di-capryl PC lipids (DCPC), that activate SPLA2 [50], are incorporated into the carrier PEG-liposomes, the permeation of calcein across the target membranes increases almost instantaneously. [Pg.48]

The release profiles suggest that the lysoPPC and PA hydrolysis products, which are formed in a 1 1 molar ratio by SPLA2, are incorporated into the target membranes [51], leading to the increase in the permeability of the target liposomal membranes. These hydrolysis products, due to their non-bilayer forming molecular shapes, induce a curvature stress [52, 53] and/or form small-scale lipid domains [33, 36], which lead to membrane defects and consequently increased membrane [Pg.48]




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Activation model

Active drug

Active model

Activity model

Biophysical

Biophysical studies

Biophysics

Drugs activity

Drugs model

Model biophysical

Model studies

Modeling studies

Systems studied

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