Correction to: Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action.

An amendment to this paper has been published and can be accessed via the original article.

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action.

BACKGROUND: Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis. RESULTS: The α-Fe2O3/γ-Fe2O3 nanocomposite (IOs) was prepared using the modified sol-gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts. CONCLUSION: Fabricated by our group α-Fe2O3/γ-Fe2O3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.

Single dose, dose-escalating trial with fozivudine tidoxil (BM 21.1290).

BACKGROUND AND OBJECTIVES: In vitro and in vivo experimental data for fozivudine tidoxil [BM21.1290 (FZD) an ether-lipid conjugate of zidovudine] have shown better efficacy, no myelotoxicity and better tolerability compared with zidovudine. Therefore, the objectives of our study were to evaluate the safety of FZD in patients with human immunodeficiency virus (HIV) infection and to establish basic pharmacokinetic data. PATIENTS AND METHODS: In a Phase I dose-escalating trial, seven different single dose applications were studied in 39 patients: 50, 100, 300, 600, 900, 1200 and 1800 mg in capsule and tablet formulations. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. Exclusion criteria were active opportunistic manifestations, concomitant zidovudine therapy and neutropenia (< 750 neutrophils/mm3). Safety parameters, 24 h plasma levels and urinary excretion were determined. RESULTS: The tolerance of FZD was excellent up to single doses of 1800 mg. In only one case, a single episode of loose stool was reproducible in a second treatment period and was therefore considered to be a probable drug-related event. In an amendment to the trial, a tablet formulation of FZD did not induce diarrhoea in this patient. FZD was available in measurable concentrations after 2 to 4 h. Maximum concentrations were reached after 4 to 8 h. After normalization for a dose of 100 mg/patient, the mean AUC was 8.6 mg x h/l and the mean Cmax was 1.13 mg/l; t1/2 was 3.78 h. Interestingly, plasma concentrations of zidovudine and zidovudine glucuronide were much lower than with equimolar zidovudine doses. CONCLUSIONS: The zidovudine conjugate FZD is safe and well tolerated at the seven doses tested. Phase II trials are warranted.

Phase I/II trial with fozivudine tidoxil (BM 21.1290): a 7 day randomized, placebo-controlled dose-escalating trial.

BACKGROUND AND OBJECTIVES: A Phase I dose-escalating trial with single doses of fozivudine tidoxil (BM21.1290; FZD), in vitro, and experimental in vivo data indicated that further investigations with this compound were warranted. Advantages of fozivudine tidoxil are the direct delivery of zidovudine monophosphate intracellularly and high concentrations in lymphatic tissues. Our objectives were to evaluate safety, tolerability and efficacy of fozivudine tidoxil in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: In a Phase I/II dose-escalating trial, three doses of fozivudine tidoxil (400, 800 or 1200 mg/day) were administered for 1 week. The study was randomized and placebo controlled. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. The exclusion criteria were active opportunistic infection and prior antiretroviral treatment. RESULTS: The tolerability of fozivudine tidoxil was excellent in all dose groups. No treatment discontinuations were necessary. Steady-state pharmacokinetics did show slightly higher concentrations as compared with levels after the first dose (20%). Viral load reduction was most pronounced in the 1200 mg/day dose group (-0.64 log). No viral load reduction was seen in the placebo group. CONCLUSIONS: The zidovudine conjugate fozivudine tidoxil is safe and well tolerated at the three doses tested. Based on the differences in molecular weights, the 1200 mg dose is roughly equivalent to 400 mg zidovudine.