The use of shear stress for targeted drug delivery

Stenosed segments of arteries significantly alter the blood flow known from healthy vessels. In particular, the wall shear stress at critically stenosed arteries is at least an order of magnitude higher than in healthy situations. This alteration represents a change in physical force and might be used as a trigger signal for drug delivery. Mechano-sensitive drug delivery systems that preferentially release their payload under increased shear stress are discussed. Therefore, besides biological or chemical markers, physical triggers are a further principle approach for targeted drug delivery. We hypothesize that such a physical trigger is much more powerful to release drugs for vasodilation, plaque stabilization, or clot lysis at stenosed arteries than any known biological or chemical one

Analyse par chromatographie gazeuse de mélanges racémiques au moyen de cyclodextrines peralkylées

Chromatographic performances of chiral capillary columns obtained by dilution in OV 1701 of permethylated and perpropylated β-cyclodextrine or the mixture of the two are compared. Attention has been paid to reproducibility of chromatographic properties after long storage under He

X-ray micro computed tomography for the visualization of an atherosclerotic human coronary artery

Atherosclerosis refers to narrowing or blocking of blood vessels that can lead to a heart attack, chest pain or stroke. Constricted segments of diseased arteries exhibit considerably increased wall shear stress, compared to the healthy ones. One of the possibilities to improve patient's treatment is the application of nano-therapeutic approaches, based on shear stress sensitive nano-containers. In order to tailor the chemical composition and subsequent physical properties of such liposomes, one has to know precisely the morphology of critically stenosed arteries at micrometre resolution. It is often obtained by means of histology, which has the drawback of offering only two-dimensional information. Additionally, it requires the artery to be decalcified before sectioning, which might lead to deformations within the tissue. Micro computed tomography (muCT) enables the three-dimensional (3D) visualization of soft and hard tissues at micrometre level. muCT allows lumen segmentation that is crucial for subsequent flow simulation analysis. In this communication, tomographic images of a human coronary artery before and after decalcification are qualitatively and quantitatively compared. We analyse the cross section of the diseased human coronary artery before and after decalcification, and calculate the lumen area of both samples

Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear- responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC- Pad formulations in human and porcine sera, along with the nanopharmaceutical- mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20 mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad- PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA

The use of shear stress for targeted drug delivery

Stenosed segments of arteries significantly alter the blood flow known from healthy vessels. In particular, the wall shear stress at critically stenosed arteries is at least an order of magnitude higher than in healthy situations. This alteration represents a change in physical force and might be used as a trigger signal for drug delivery. Mechanosensitive drug delivery systems, that preferentially release their payload under increased shear stress, are discussed. Therefore, besides biological or chemical markers, physical triggers are a further principle approach for targeted drug delivery. We hypothesize that such physical trigger is much more powerful to release drugs for vasodilation, plaque stabilization or clot lysis at stenosed arteries than any known biological or chemical ones