Author: Eijsman, Leon ; Emmens, Reindert W ; Niessen, Hans W M ; Krijnen, Paul A J ; van Hinsbergh, Victor W M ; van Dijk, Annemieke ; Vonk, Alexander B A ; Sipkens, Jessica A ; Kupreishvili, Koba ; Stooker, Wim ; Quax, Paul H

BACKGROUNDArterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory phospholipase A₂ (sPLA₂-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA₂-IIA herein.METHODSThe effects of PX-18, an inhibitor of both sPLA₂-IIA and apoptosis, on residual endothelium and the presence of sPLA₂-IIA were studied in human saphenous vein segments (n = 6) perfused at arterial blood pressure with autologous blood for 6 hrs.RESULTSThe presence of PX-18 in the perfusion blood induced a significant 20% reduction in endothelial cell loss compared to veins perfused without PX18, coinciding with significantly reduced sPLA₂-IIA levels in the media of the vein graft wall. In addition, PX-18 significantly attenuated caspase-3 activation in human umbilical vein endothelial cells subjected to shear stress via mechanical stretch independent of sPLA₂-IIA.CONCLUSIONSIn conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure-induced death, possibly also independent of sPLA₂-IIA inhibition.

01 May 2011·Die Pharmazie

Nanostructured lipid carriers as delivery system for the phopholipase A2 inhibitors PX-18 and PX-13 for dermal application.

Article

Author: Volz, I ; Schmidt, C ; Pardeike, J ; Müller, R H

PX-18 and PX-13 are secretory phospholipase A2-IIA (sPLA2-IIA) inhibitors. An increased expression of sPLA2 in psoriatic skin has been reported. The selective inhibition of this enzyme is a new therapeutic approach. For dermal application PX-18 and PX-13 have been loaded to Nanostructured lipid carriers (NLC). The PX-18-loaded and PX-13-loaded NLC possessed an average particles size of about 250 nm, a narrow particle size distribution (PI < 0.2), a high entrapment efficiency as well as a good physical stability, as already indicated by their high zeta potential. Both NLC formulations have been incorporated into a hydroxyethyl cellulose gel and an o/w cream. In the gel and in the o/w cream PX-18-loaded and PX-13-loaded NLC showed a good physical stability. Neither aggregation nor dissolution of NLC took place.

01 May 2010·International Journal of PharmaceuticsQ2 · MEDICINE

Nanosuspensions: A promising formulation for the new phospholipase A2 inhibitor PX-18

Q2 · MEDICINE

Article

Author: Rainer H. Müller ; Jana Pardeike

PX-18 is a new highly potent phospholipase A(2) inhibitor with a poor aqueous solubility. Therefore, it was formulated as nanosuspensions with an active content of 1% (w/w), 5% (w/w) and 10% (w/w) using high-pressure homogenization. By contact angle measurements on compressed discs of PX-18, Tween 80 was identified as best wetting agent of PX-18 and therefore used to stabilize the nanosuspensions. The achieved particle size of all nanosuspensions was well in the nanometer range. For the 1% (w/w) PX-18 nanosuspension an average particle size below 50 nm was measured by photon correlation spectroscopy (PCS). A good reproducibility of the mean particle size was found in between different batches. As postulated by the zeta potential of the nanosuspensions, a good physical stability over an observation period of 180 days was obtained when stored at 5+/-3 degrees C. PX-18 formulated as nanosuspensions was chemically stabile. An increase in saturation solubility was found after formulating PX-18 as nanosuspension compared to bulk material, favourable for increasing bioavailability.

100 Deals associated with PX-18 (Virginia Commonwealth University)

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Infections	Discovery	US	Virginia Commonwealth University	-
Perioperative ischaemia	Discovery	US	Virginia Commonwealth University	-

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