Search Results (14)

Curcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the solvent evaporation method and were characterized by dynamic and electrophoretic light scattering, transmission electron (TEM) and atomic force (AFM) microscopy. The average particle size was 200 nm, and the ζ-potential was −4 mV. Curcumin-release studies showed that nanoparticles are stable in aqueous solutions. An in vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently, and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to free curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. The median lethal dose was determined in an acute toxicity assay on zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment. Full article

One-pot synthesis of colloidal Au/ZnO and Ag/ZnO nanohybrid structures was carried out. The copolymers of maleic acid—poly(N-vinyl-2-pyrrolidone-alt-maleic acid), poly(ethylene-alt-maleic acid), or poly(styrene-alt-maleic acid) were used as templates for the sorption of cations of metals-precursors and stabilization of the resulting nanoheterostructures. Simultaneous production of two types of nanoparticles has been implemented under mild conditions in an aqueous alkaline medium and without additional reagents. Equimolar ratios of the metal cations and appropriate load on all copolymers were used: molar ratio of maleic acid monomeric units of copolymer/gold (silver)cations/zinc cations was 1/0.15/0.23 (1/0.3/0.15). The process of obtaining the heterostructures was studied using UV-Vis spectroscopy. The kinetics of the formation of heterostructures was influenced by the nature of the maleic acid copolymer and noble metal cations used. A high reaction rate was observed in the case of using zinc and gold cations-precursors and a copolymer of maleic acid with N-vinylpyrrolidone as a stabilizer of nanoparticles. The structure of the synthesized polymer-stabilized heterostructures was studied using instrumental methods of analysis—XPS, FTIR, PXRD, and TEM. Under the conditions used, stable colloidal solutions of heterodimers were obtained, and such structure can be converted to a solid state and back without loss of properties. Full article

The progress achieved in recent years in the biomedical field justifies the objective evaluation of new techniques and materials obtained by using silver in different forms as metallic silver, silver salts, and nanoparticles. Thus, the antibacterial, antiviral, antifungal, antioxidant, and anti-inflammatory activity of silver nanoparticles (AgNPs) confers to newly obtained materials characteristics that make them ideal candidates in a wide spectrum of applications. In the present study, the use of hydroxypropyl methyl cellulose (HPMC) in the new formulation, by embedding AgNPs with antibacterial activity, using poly(N-vinylpyrrolidone) (PVP) as a stabilizing agent was investigated. AgNPs were incorporated in HPMC solutions, by thermal reduction of silver ions to silver nanoparticles, using PVP as a stabilizer; a technique that ensures the efficiency and selectivity of the obtained materials. The rheological properties, morphology, in vitro antimicrobial activity, and stability/catching of Ag nanoparticles in resulting HPMC/PVP-AgNPs materials were evaluated. The obtained rheological parameters highlight the multifunctional roles of PVP, focusing on the stabilizing effect of new formulations but also the optimization of some properties of the studied materials. The silver amount was quantified using the spectroscopy techniques (energy-dispersive X-ray fluorescence (XRF), energy-dispersive X-ray spectroscopy (EDX)), while formation of the AgNPs was confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Also, the morphological examination (Atomic Force Microscopy (AFM) and Scanning electron microscopy (SEM)) by means of the texture roughness parameters has evidenced favorable characteristics for targeted applications. Antibacterial activity was tested against Escherichia coli and Staphylococcus aureus and was found to be substantially improved was silver was added in the studied systems. Full article

An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid—namely, p(VP-AA)-OD6000 (p(VP-AA))—was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells’ viability at the higher concentrations of 0.033 and 0.066 mg/mL (p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized (p = NS) did not affect individual adhesion molecules’ expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations. Full article

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core–shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure. Full article

This study was focused on synthesizing, characterizing, and evaluating the antimicrobial effect of polymer nanoparticles (NPs) loaded with ampicillin. For this, the NPs were produced through polymeric self-assembly in aqueous media assisted by high-intensity sonication, using anionic polymers corresponding to the sodium salts of poly(maleic acid-co-vinylpyrrolidone) and poly(maleic acid-co-vinylpyrrolidone) modified with decyl-amine, here named as PMA-VP and PMA-VP-N10, respectively. The polymeric NPs were analyzed and characterized through the formation of polymeric pseudo-phases utilizing pyrene as fluorescent probe, as well as by measurements of particle size, zeta potential, polydispersity index, and encapsulation efficiency. The antimicrobial effect was evaluated by means of the broth microdilution method employing ampicillin sensitive and resistant Staphylococcus aureus strains. The results showed that PMA-VP and PMA-VP-N10 polymers can self-assemble, forming several types of hydrophobic pseudo-phases with respect to the medium pH and polymer concentration. Likewise, the results described that zeta potential, particle size, polydispersity index, and encapsulation efficiency are extremely dependent on the medium pH, whereas the antimicrobial activity displayed an interesting recovery of antibiotic activity when ampicillin is loaded in the polymeric NPs. Full article

Nanoparticles are increasingly utilized as drug delivery agents. Previously, we have developed a drug delivery system based on amphiphilic derivatives of poly-N-vinylpyrrolidone (PVP-OD4000) with excellent biocompatibility. In the current study, we assessed the pharmacokinetics, anti-inflammatory profile, and ulcerogenic potential of indomethacin (IMC)-loaded PVP-OD4000 nanoparticles compared to the free drug. Wistar male rats were utilized for a pharmacokinetics study and an anti-inflammatory study. Loaded IMC exhibited a slower elimination rate (p < 0.05) and a higher blood plasma concentration at 8 and 24 h after intraperitoneal injection compared with free IMC. In addition, decreased uptake of loaded IMC in the liver and kidney compared to free IMC (p < 0.05) was detected. Furthermore, PVP-OD4000 nanoparticles loaded with IMC showed an enhanced anti-inflammatory effect compared to free IMC (p < 0.05) in carrageenan-induced and complete Freund’s adjuvant-induced–(CFA) sub-chronic and chronic paw edema treatment (p < 0.01; p < 0.01). Notably, upon oral administration of loaded IMC, animals had a significantly lower ulcer score and Paul’s Index (3.9) compared to the free drug (p < 0.05). The obtained results suggest that IMC loaded to PVP nanoparticles exhibit superior anti-inflammatory activity in vivo and a safe gastrointestinal profile and pose a therapeutic alternative for the currently available NSAIDs’ administration. Full article

Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery. Full article

Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were proposed earlier as a new drug delivery system. In the current work, we study the antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with the antitumor receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP polymer was synthesized by the earlier developed one-step technique (Kulikov et al., Polym. Sci. Ser. D, 2017). To stabilize Amph-PVP associates, the hydrophobic core was loaded with the model substance prothionamide. For the covalent conjugation with DR5-B, the hydrophilic ends of polymeric chains were modified with maleimide, and a DR5-B N-terminal amino acid residue valine was mutated to cysteine (DR5-B/V114C). DR5-B/V114C was conjugated to the surface of polymeric micelles by the selective covalent interaction of N-terminal cysteine residue with maleimide on Amph-PVP. The cytotoxicity of DR5-B-conjugated Amph-PVP polymeric nanoparticles was investigated in 3D multicellular tumor spheroids (MCTS) of human colon carcinoma HCT116 and HT29 cells, generated by the RGD-induced self-assembly technique (Akasov et al., Int. J. Pharm., 2016). In DR5-B-sensitive HCT116 MCTS, the P-DR5-B activity slightly increased compared to that of DR5-B. However, in DR5-B-resistant HT29 MCTS, P-DR5-B significantly surpassed DR5-B in the antitumor activity. Thus, the conjugation of DR5-B with the Amph-PVP nanoparticles enhanced its tumor-cell killing capacity. In the current study, we obtain a new nano-scaled delivery system based on Amph-PVP self-aggregates coated with covalently conjugated antitumor DR5-specific cytokine DR5-B. P-DR5-B overcomes DR5-B-resistance of the human colon carcinoma MCTS in vitro. This makes Amph-PVP polymeric nanoparticles a prospective and versatile nano-scaled delivery system for the targeted proteins. Full article

Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. The aim of the study was to fabricate Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) variant DR5-B and to evaluate their in vitro cytotoxicity in 3D tumor spheroids. The Amph-PVP nanoparticles were obtained from a 1:1 mixture of unmodified and maleimide-modified polymeric chains, while DR5-B protein was modified by cysteine residue at the N-end for covalent conjugation with Amph-PVP. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. The cytotoxicity of the nanoparticles was investigated in human cell lines, namely breast adenocarcinoma MCF-7 and colorectal carcinomas HCT116 and HT29. Notably, DR5-B conjugation with Amph-PVP nanoparticles sensitized resistant multicellular tumor spheroids from MCF-7 and HT29 cells. Taking into account the nanoparticles loading ability with a wide range of low-molecular-weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, we suggest further development to obtain a versatile system for targeted drug delivery into tumor cells. Full article

Gold nanoparticles (AuNPs) were synthesized and stabilized using the one-pot method and growth seeding, through utilization of synthetic polymers, including poly(N-vinylpyrrolidone) (PVP), poly(ethylene glycol) (PEG), and poly(vinylcaprolactame) (PVCL), as well as natural polysaccharides, including gellan, welan, pectin, and κ-carrageenan. The absorption spectra, average hydrodynamic size, ζ-potential, and morphology of the gold nanoparticles were evaluated based on various factors, such as polymer concentration, molecular mass of polymers, temperature, and storage time. The optimal polymer concentration for stabilization of AuNPs was found to be 4.0 wt % for PVP, 0.5 wt % for gellan, and 0.2 wt % for pectin, welan, and κ-carrageenan. The values of the ζ-potential of polymer-stabilized AuNPs show that their surfaces are negatively charged. Most of the AuNPs are polydisperse particles, though very monodisperse AuNPs were detected in the presence of a 0.5 wt % gellan solution. At a constant polymer concentration of PVP (4 wt %), the average size of the PVP–AuNPs decreased with the decrease of molecular weight, and in the following order: PVP 350 kDa (~25 nm) > PVP 40 kDa (~8 nm) > PVP 10 kDa (~4 nm). The combination of Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy revealed that the functional groups of polymers that are responsible for stabilization of AuNPs are lactam ring in PVP, carboxylic groups in gellan and welan, esterified carboxylic groups in pectin, and SO₂ groups in κ-carrageenan. Viscometric and proton nuclear magnetic resonance (¹H NMR) spectroscopic measurements showed that the temperature-dependent change in the size of AuNPs, and the gradual increase of the intensity of AuNPs at 550 nm in the presence of gellan, is due to the rigid and disordered conformation of gellan that affects the stabilization of AuNPs. The AuNPs synthesized in the presence of water-soluble polymers were stable over a period of 36 days. Preliminary results on the synthesis and characterization of gold nanorods stabilized by polymers are also presented. Full article

Non-aqueous dispersions (NAD) with two types of polymeric nanoparticles (NPs), such as hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic cross-linked poly(vinylpyrrolidone) (PNVP), were synthesized in the present study starting from monomer-in-silicone oil (PDMS) polymerizable non-aqueous emulsions stabilized with the same tailor-made PDMS-based block copolymer. These NPs were loaded with CCisplatin, an antitumoral model drug, directly from the emulsion polymerization step, and it was observed that the presence of the drug leads only to a slight increase of the NPs size, from 120 to 150 nm. The drug release kinetics was evaluated at 37 °C in phosphate buffer at pH = 7.4 and it appeared that the drug release rate from the hydrophilic cross-linked PNVP-based NPs is higher than that from the hydrophobic PCL-based NPs. Moreover, haemolysis tests revealed the fact that these two types of NPs have a good compatibility with the blood. Furthermore, for both the free and drug-loaded NPs, the in vitro cytotoxicity and apoptosis was studied on two types of cancer cell lines, such as MCF-7 (breast cancer cell line) and A-375 (skin cancer cell line). Both types of NPs had no cytotoxic effect but, at a concentration of 500 μg/mL, presented an apoptotic effect similar to that of the free drug. Full article

In this study, a low concentration (10 μg·mL⁻¹) of poly(N-vinylpyrrolidone) (PVP)-coated silver nanoparticles (AgNPs) were deposited by spray and exhaustion (30, 70 and 100 °C) methods onto untreated and dielectric barrier discharge (DBD) plasma-treated polyamide 6,6 (PA66) fabric. DBD plasma-treated samples showed higher AgNP deposition than untreated ones for all methods. After five washing cycles, only DBD plasma-treated samples displayed AgNPs on the fabric surface. The best-performing method was exhaustion at 30 °C, which exhibited less agglomeration and the best antibacterial efficacy against S. aureus (4 log reduction). For E. coli, the antimicrobial effect showed good results in all the exhaustion samples (5 log reduction). Considering the spray method, only the DBD plasma-treated samples showed some bacteriostatic activity for both strains, but the AgNP concentration was not enough to have a bactericidal effect. Our results suggest DBD plasma may be a low cost and chemical-free method for the preparation of antibacterial textiles, allowing for the immobilization of a very low—but effective—concentration of AgNPs. Full article