Biodegradable poly(l-lactide)/calcium phosphate composites with improved properties for orthopedics: Effect of filler and polymer crystallinity.

Biodegradable poly(l-lactide)/calcium phosphate composites are promising materials for fabrication of bone fixation implants with improved properties. Multistage compounding was proposed as an efficient method for the preparation of biodegradable poly(l-lactide)/calcium phosphate composites with submicron filler dispersion and mechanical characteristics similar to native bone. The improvement of the characteristics is caused both by the filler itself and by the increase of polymer crystallinity due to the nucleation effect. The technique allows to fabricate biodegradable composites with controlled properties by varying concentration and type of the filler as well as degree of PLLA matrix crystallinity. Animal studies revealed that all the composites were biocompatible and non-toxic.

Lupane-type conjugates with aminoacids, 1,3,4- oxadiazole and 1,2,5-oxadiazole-2-oxide derivatives: Synthesis, anti-inflammatory activity and in silico evaluation of target affinity.

With the purpose to improve anti-inflammatory activity, the impact of introduction of 1,2,5- and 1,3,4-oxadiazole fragments to betulonic acid core as well as hybrids tethered with short ω-amino acids has been studied. The anti-inflammatory activity of synthesized compounds was tested in vivo using models of inflammation induced by concanavalin A and histamine. The majority of new compounds demonstrated higher anti-inflammatory activity compared with starting betulonic acid. To confirm the molecular targets of new derivatives in NRf2 and NFκB pathways the docking at Kelch and BTB active sites of Keap1 as well as IKK was done. The novelty of the present work is the development of new class of low toxic anti-inflammatory substances consisting of amino acid-linked betulonic acid - oxadiazole conjugates. These compounds can be considered as prospective chemopreventive agents.

Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice.

Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a 'plus-maze' test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis.

Analgesic effect from Ibuprofen nanoparticles inhaled by male mice.

BACKGROUND: Aerosol lung administration is a convenient way to deliver water-insoluble or poorly soluble drugs, provided that small-sized particles are generated. Here, for the outbred male mice, we show that the pulmonary administration of ibuprofen nanoparticles requires a dose that is three to five orders of magnitude less than that for the orally delivered particles at the same analgesic effect. METHOD: The aerosol evaporation-condensation generator consisted of a horizontal cylindrical quartz tube with an outer heater. Argon flow was supplied to the inlet and aerosol was formed at the outlet. The particle mean diameter and number concentration varied from 10 to 100 nm and 10(3)-10(7) cm(-)3, respectively. The analgesic action and side pulmonary effects caused by the inhalation of ibuprofen nanoparticles were investigated. RESULTS: The chemical composition of aerosol particles was shown to be identical with the maternal drug. Using the nose-only exposure chambers, the mice lung deposition efficiency was evaluated as a function of the particle diameter. CONCLUSIONS: The dose-dependent analgesic effect of aerosolized ibuprofen was studied in comparison with the oral treatment. It was found that the dose for aerosol treatment is three to five orders of magnitude less than that required for oral treatment at the same analgesic effect. Accompanying effects were moderate venous hyperemia and some emphysematous signs.