Application of Magnetic Nanoparticles in Pharmaceutical Sciences

# The Author(s) 2010. This article is published with open access at Springerlink.com KEY WORDS magnetic beads. magnetic bioseparation. magnetic nanoparticle

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor — NARCOTIC trial

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’. Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest

Background: Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitantdual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI.Methods: In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose.Results: In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0–12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6–24] vs. 4 [2–12] h, p = 0.01).Conclusions: Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. Trial registration: ClinicalTrials.gov Identifier: NCT0261193

Synthesis of magnetic nanoparticles with surface modified with chitosan and poly(acrylic acid) blends for biomedical application

In recent years, the synthesis and characterization of nanoparticles have been the focus of intensive research. This type of nanoparticles have been highly employed in chemistry and biomedical applications such as magnetic hyperthermia, catalysis, diagnostic agent, and especially for biomolecule immobilization. The properties of the magnetic materials depends on the stabilizer type, which affect on covering surface. In this study the synthesis of new type of chitosan (CS) and poly (acrylic acid) (PAA) coated nanoparticles by photopolymerization is presented (Fig. 1) [1-3]. Pure monomer of acrylic acid were subjected to photopolymerization, while the photopolymerization kinetics was followed by FTIR spectroscopy. The band corresponding to the C=C stretching vibrations has been selected for calculation of conversion degree of monomer. The structure of prepared magnetic material was processed by ATR-FTIR spectroscopy and XRD analysis. The morphology and size of the prepared nanoparticles were characterized by transmission electron microscopy. The amount of free amino groups on the surface of magnetic nanoparticles was estimated by the ninhydrin method. The activity, reusability, and the amount of immobilizer lipase were determined. [1] Chełminiak D., Ziegler-Borowska M., Kaczmarek H., Mater. Lett. 164 (2016) 464-467. [2] Ziegler-Borowska M., Siódmiak T., Chełminiak D., et. al. Appl. Surf. Sci. 288 (2014) 641-648. [3] Ziegler-Borowska M., Chełminiak D., Siódmiak T., et. al. Mater. Lett. 132 (2014) 63-65. Acknowledgements The project was supported by research grant: National Science Centre 2014/15/B/NZ7/00972

Chitosan–Collagen Coated Magnetic Nanoparticles for Lipase Immobilization—New Type of “Enzyme Friendly” Polymer Shell Crosslinking with Squaric Acid

This article presents a novel route for crosslinking a polysaccharide and polysaccharide/protein shell coated on magnetic nanoparticles (MNPs) surface via condensation reaction with squaric acid (SqA). The syntheses of four new types of collagen-, chitosan-, and chitosan–collagen coated magnetic nanoparticles as supports for enzyme immobilization have been done. Structure and morphology of prepared new materials were characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR), XRD, and TEM analysis. Next, the immobilization of lipase from Candida rugosa was performed on the nanoparticles surface via N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC)/N-hydroxy-succinimide (NHS) mechanism. The best results of lipase activity recovery and specific activities were observed for nanoparticles with polymer shell crosslinked via a novel procedure with squaric acid. The specific activity for lipase immobilized on materials crosslinked with SqA (52 U/mg lipase) was about 2-fold higher than for enzyme immobilized on MNPs with glutaraldehyde addition (26 U/mg lipase). Moreover, a little hyperactivation of lipase immobilized on nanoparticles with SqA was observed (104% and 112%)

Baseline characteristics of study participants.

<p>Baseline characteristics of study participants.</p

Bioavailability of ticagrelor and AR-C124910XX over time in patients with STEMI and NSTEMI.

<p>Plasma concentrations of (A) ticagrelor and (B) AR-C124910XX during the first 6 h after oral administration of a 180 mg ticagrelor loading dose in patients with STEMI and NSTEMI. NSTEMI: non-ST-elevation myocardial infarction, STEMI: ST-elevation myocardial infarction.</p

Platelet reactivity over time in STEMI and NSTEMI patients.

<p>Platelet reactivity evaluated with (A) the VASP assay and (B) Multiplate at baseline, and at 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, and 12 h after administration of a 180 mg ticagrelor loading dose in patients with STEMI and NSTEMI. NSTEMI: non-ST-elevation myocardial infarction, STEMI: ST-elevation myocardial infarction, VASP: vasodilator-stimulated phosphoprotein.</p

Prevalence of high platelet reactivity over time in STEMI and NSTEMI patients.

<p>Proportion of patients with high platelet reactivity assessed with (A) the VASP assay and Multiplate (B) at baseline, and at 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, and 12 h after administration of a 180 mg ticagrelor loading dose in patients with STEMI and NSTEMI. HPR: high platelet reactivity, NSTEMI: non-ST-elevation myocardial infarction, STEMI: ST-elevation myocardial infarction, VASP: vasodilator-stimulated phosphoprotein.</p