Mg.ATP-decorated ultrafine magnetic nanofibers: A bone scaffold with high osteogenic and antibacterial properties in the presence of an electromagnetic field.

In this study, ultrafine magnetic nanofibers were developed for bone regeneration purposes. Nanofibers were acquired by electrospinning using a two-component nanofiber matrix (CP: chitosan (Cs) and polyvinyl alcohol (PVA)) containing different concentrations of succinate conjugated-magnetic hydroxyapatite nanocomposites (SMHA). Hybrid nanofibers (CP&SMHA) containing 5 mg ml-1 of SMHA nanocomposite showed well-defined properties in terms of physicochemical properties and cell behavior. Then, they were modified with adenosine 5'-triphosphate (ATP) and Mg2+ ions. The initial adhesion of mesenchymal stem cells and their proliferation rate on the surface of modified nanofibers (Mg.ATP.CP&SMHA) were significantly increased as compared to those of bare nanofibers. Analysis of common osteogenic markers such as alkaline phosphatase activity and the expression of Runt-related transcription factor 2 and osteocalcin confirmed the osteogenic efficacy enhancement of CP&SMHA nanofibers when they were functionalized with ATP and Mg2+. The utilization of the antagonist of purine receptor, P2X7, revealed that this receptor has a major role in the osteogenesis process induced by Mg.ATP.CP&SMHA. Moreover, the results showed that cell adhesion, proliferation, and differentiation improved as nanofibers were under the influence of the electromagnetic field (EMF), displaying synergistic effects in the process of bone formation. Mg.ATP.CP&SMHA also showed an antibacterial effect against gram-negative and gram-positive bacteria, Escherichia coli and Staphylococcus aureus, respectively. Considering the high osteogenic potential and antibacterial activity of Mg.ATP.CP&SMHA nanofibers particularly in combination with EMF, it can serve as a great candidate for use in bone tissue engineering applications.

Mesoporous superparamagnetic hydroxyapatite nanocomposite: A multifunctional platform for synergistic targeted chemo-magnetotherapy.

In the present study, the aim was to develop a magneto-responsive nanocomposite for application in drug delivery by the integration of magnetic nanoparticles into an inorganic architecture, hydroxyapatite. The magnetic mesoporous hydroxyapatite nanocomposites, MMHAPs, were synthesized using a template-free method and fully characterized by XRD, FT-IR, TEM, FE-SEM, VSM, ICP, BET, and UV-Vis spectroscopy. MMHAPs exhibited a rod-like shape with a structure of large mesopores and high surface area. A sample of the nanocomposites with well-defined properties, MMHAP(2), was selected as a carrier for delivery of chemotherapy drug, doxorubicin (Dox). Then, it was coated with polyethylene glycol (P) and folic acid (F), providing aqueous stability and tumor targeting, respectively. The evaluation of drug release profile revealed that the release of drug occurs in a time-staggered manner under low pH conditions, which simulate the internal condition of lysosome. More important, a significant drug release was observed under a static magnetic field (SMF), displaying a magnetically triggered release. According to the toxicity assessment, MMHAP(2) did not show any noticeable toxic effect against the tumor cells (Saos-2) and normal cells (HEK-293) up to 100 µg ml-1 in the presence or absence of SMF. In contrast, the drug-loaded nanocomposite, F.P.D@MMHAP(2), possesses high antitumor efficacy particularly in the presence of SMF. Moreover, it was found that the cellular internalization of F.P.D@MMHAP(2) could be increased by SMF, providing therapeutic efficiency enhancement. The high cytotoxic effect of F.P.D@MMHAP(2) with the help of SMF caused apoptosis in the tumor cells, which was preceded by a disturbance in the intracellular redox state and then caspase activation. Based on the data obtained, F.P.D@MMHAP(2) is a pH- and magneto-responsive platform opening up a new perspective in terms of its exploitation in cancer therapy.

Alleviation of Morphine Withdrawal Signs but Not Tolerance by the Essential Oil of Kelussia odoratissima Mozaff.

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2 h after the final morphine injection. Repeated injection of the EO of K. odoratissima (5 and 10 mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100 mg/kg) of the EO on day 5, 1 h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of the K. odoratissima did significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection with K. odoratissima is indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain.