Tigapotide Triflutate

In this work, tigapotide (PCK3145) was incorporated into novel block copolymer polyelectrolyte nanocarriers in order to maximize the advantages of the delivery process and possibly its biological properties. PCK3145 was incorporated into complexes with the block polyelectrolyte poly(vinyl benzyl trimethylammonium chloride)-b-poly(oligo(ethylene glycol) methyl ether methacrylate) (PVBTMAC-POEGMA). Light scattering techniques (dynamic, static and electrophoretic) are used in order to examine the size, the size distribution, the morphology and the z-potential of the nanocarriers incorporating PCK3145 in different aqueous media. The concentration of PVBTMAC-POEGMA is kept constant throughout the series of aqueous solutions of different ionic strength investigated. The values of the scattering intensity, I90, which is proportional to the mass of the species in solution, increase gradually as a function of CPCK3145 providing proof of the occurring complexation. It was shown that the structure and solution behavior of the formed complexes depend on the ratio of the two components, as well as on the pH and the ionic strength of the solution. The physicochemical characteristics of the complexes, as a function of PCK concentration, remained unaffected at higher ionic strength (0.154 M). This investigation provides interesting and useful new insights into the interaction mechanism between oppositely charged block polyelectrolytes and therapeutic peptides.

PCK3145 is a synthetic peptide, derived from the Prostate Secreted Protein 94 (PSP94), with promising in vitro and animal in vivo results in prostate cancer. The aim of the present study was to develop and validate a fast and robust ultra‐high‐performance liquid chromatography with ultraviolet detection for the determination of PCK3145 in human plasma which would be suitable for the assessment of PCK3145 stability to proteolytic degradation. Following protein precipitation, chromatographic separation was carried out on an Aeris Peptide C18 column with mobile phase consisting of acetonitrile–water at a flow‐rate of 0.50 mL/min. The calibration curve was linear over the range 0.50–20.00 μg/mL. Intra‐ and inter‐day percentage relative standard deviation and relative error were ≤10%. The limit of detection and the lower limit of quantification were 0.15 and 0.50 μg/mL, respectively. Recovery of PCK3145 from human plasma was ≥96%. The peptide presented high stability in whole blood and in human plasma (>98% intact peptide after 24 h incubation at 37°C in human plasma), which represents a distinctive advantage in the therapeutic use of the compound. This is the first validated UHPLC method for the determination of PCK3145 reported, and it was successfully applied in the study of the proteolytic stability of PCK3145 in human plasma ex vivo. Copyright © 2016 John Wiley & Sons, Ltd.