This finding opens an intriguing possibility of intranuclear delivery by merely tailoring the size of polymeric carriers, thus promising a new approach for cancer therapies.
Nanoparticles (NPs) produced from amphiphilic derivatives of poly-N-vinylpyrrolidone (Amph-PVP), composed of various molecular weight polymeric hydrophilic fragments linked into hydrophobic n-alkyl chains of varying lengths, were previously shown to exert excellent biocompatibility. Although routes of administration can be different, finally, most nanosystems enter the blood circulation or lymphatic vessels, and by this, they establish direct contact with endothelial cells. In this study, Amph-PVP NPs and fluorescently labeled Amph-PVP-based NPs, namely "PVP" NPs (Amph-PVP-NPs (6000 Da) unloaded) and "F"-NPs (Amph-PVP-NPs (6000 Da) loaded with fluorescent FITC), were synthesized to study Amph-PVP NPs interactions with HMEC-1 endothelial cells. PVP NPs were readily uptaken by HMEC-1 cells in a concentration-dependent manner, as demonstrated by immunofluorescence imaging. Upon uptake, the FITC dye was localized to the perinuclear region and cytoplasm of treated cells. The generation of lipopolysaccharide (LPS)-induced activated endothelium model revealed an increased uptake of PVPNPs, as shown by confocal microscopy. Both unloaded PVP NPs and F-NPs did not affect EC viability in the 0.01 to 0.066 mg/mL range. Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon PVPNPs treatment by assessing the expression of their E-Selectin, ICAM-1, and VCAM-1 adhesion receptors. None of the adhesion molecules were affected by NP treatments of both activated by LPS and nonactivated HMEC-1 cells, at the utilized concentrations (p = NS). In this study, PVP (6000 Da) NPs were used to encapsulate indomethacin, a widely used anti-inflammatory drug. The synthesized drug carrier complex did not affect HMEC-1 cell growth and expression of E-selectin, ICAM-1, and VCAM-1 adhesion receptors. In summary, PVP-based NPs are safe for use on both basal and activated endothelium, which more accurately mimics pathological conditions. Amph-PVP NPs are a promising drug delivery system.
Nanoparticles can experience numerous impacts during storage or after intravenous administration resulting in disassembly and/or drug leakage and affecting their efficiency as drug delivery systems. In this study, this crucial issue was addressed by investigating the stability of amphiphilic poly-N-vinylpyrrolidone derivative nanocarriers in blood serum, against destabilizing agents and during long-term storage. All amphiphilic poly-N-vinylpyrrolidone derivative nanoparticles prepared in this study were found to possess sizes less than 150 nm, narrow size distribution, spherical morphology, and a slightly negative surface charge. These nanoparticles could efficiently entrap hydrophobic substances (pyrene and curcumin) while retaining excellent compatibility with red blood cells. Moreover, our studies demonstrate the stability of the nanoparticles during long-term storage and upon dilution with body liquids enhancing their potential as stable in vivo carriers, which is critically important for intravenous drug delivery applications. All properties were found to strongly depend on the ratio between the hydrophobic and the hydrophilic moiety of the polymers under study.
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