Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC_0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.     

Synthesis of 4-Aryl-6-oxo-5-cyano-1,6-dihydropyridine-2-carboxylic Acids and Their Methyl Esters by Reacting Methyl Acylpyruvates with Malononitrile and Cyanoacetamide

Russian Journal of General Chemistry - A series of new methyl 4-aryl-6-oxo-5-cyano-1,6-dihydropyridine-2-carboxylates and 4-aryl-6-oxo-5-cyano-1,6-dihydropyridine-2-carboxylic acids were...     

Synthesis and antioxidant activity of new hydroxy derivatives of chalcones

New hydroxy derivatives of chalcones obtained via a condensation of 3-acetyl-2H-chromen-2-one with 2,4-dihydroxy- and 4-hydroxy-benzaldehydes and via an aldol crotonic condensation of methyl N-(4-acetylphenyl)carbamate with 4-hydroxy-3,5-di(tert-butyl)benzaldehyde have been isolated and characterized. A wide range of promising biological activity of the synthesized compounds, including the radical scavenging and antioxidant ones, was predicted by the in silico method. The anti- and pro-oxidant activities in model systems of peroxidation of cis-9-octadecenoic (oleic) acid and lipids from the liver homogenate of tilapia were estimated in vitro. The presence of sterically hindered hydroxy groups and a chromene moiety provides the prolonged antioxidant activity of new hydroxy derivatives of chalcones.

     

Reductive amination of ferrocenylformylpyrazoles

1-Aryl-3-ferrocenyl-4-formylpyrazoles were obtained from appropriate acetylferrocene arylhydrazones by the Vilsmeier—Haack reaction. Direct reductive amination of the resulting aldehydes with primary and secondary amines and amino acid esters in the presence of NaBH(OAc)₃ was studied.     

The optical module of Baikal-GVD

In April 2015, the first cluster of Baikal-GVD was deployed in Lake Baikal and put into operation. It comprises eight strings. Each string consists of 24 optical modules. An optical module is a detection element of Baikal-GVD; it includes a Hamamatsu R7081-100 photomultiplier tube with a high quantum sensitivity. We describe the design of the optical module, the front-end electronics, and the laboratory characterization and calibration.     

Epitaxial gallium oxide on a SiC/Si substrate

Well-textured gallium oxide β-Ga₂O₃ layers with a thickness of ~1 μm and a close to epitaxial layer structure were grown by the method of chloride vapor phase epitaxy on Si(111) wafers with a nano-SiC buffer layer. In order to improve the growth, a high-quality silicon carbide buffer layer ~100 nm thick was preliminarily synthesized by the substitution of atoms on the silicon surface. The β-Ga₂O₃ films were thoroughly investigated using reflection high-energy electron diffraction, ellipsometry, X-ray diffraction, scanning electron microscopy, and micro-Raman spectroscopy. The investigations revealed that the films are textured with a close to epitaxial structure and consist of a pure β-phase Ga₂O₃ with the (\(\overline 2 01\)) orientation. The dependence of the dielectric constant of epitaxial β-Ga₂O₃ on the photon energy ranging from 0.7 to 6.5 eV in the isotropic approximation was measured.     

Relationship between the aggregation of nanoparticles bearing zinc ions and cytotoxicity and morphology of blood cells

The effect of nanoparticles bearing magnetic and nonmagnetic zinc nuclei on lymphocytes from healthy donors and leukemic cells of patients (15–20 years old) with acute B-lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML) was considered. The studies by confocal and fluorescence microscopy showed an apoptotic effect of nanoparticles bearing zinc ions. An increase in the aggregation of the nanoparticles and cell self-aggregation, resulting in a decrease in cytotoxicity, were observed in the case of the magnetic isotope. In spite of this, cell apoptosis under the action of even aggregated nanoparticles bearing magnetic ⁶⁷Zn was significantly higher than the apoptosis with lymphocytes of healthy donors and with nanoparticles bearing zinc of the total isotope composition.     

Kinetic stability of substituted tetrapyrazinoporphyrazines in a system nitrogen base-dimethylsulfoxide

The state of tetra(5-tert-butylpyrazino)porphyrazine, octaethyltetrapyrazinoporphyrazine, octaphenyltetrapyrazinoporphyrazine in DMSO medium was studied. It was found that the complexes formed with the proton transfer exhibit a relatively high stability. In strong basic media these complexes are kinetically unstable. The influence of the nature of cyclic and acyclic nitrogen-containing bases, as well as the influence of NH-acidity of the porphyrazine macrocycle on the rate and activation parameters of decomposition of the proton-transfer complexes of tetra(5-tert-butylpyrazino)porphyrazine, octaethyltetrapyrazinoporphyrazine, and octaphenyltetrapyrazinoporphyrazine was established.