Trapping tetracycline-loaded nanoparticles into polycaprolactone fiber networks for periodontal regeneration therapy

The controlled delivery of antibiotics, anti-inflammatory agents, or chemotherapeutic agents to the periodontal site is a recognized strategy to improve the efficiency of regenerative processes of hard tissues. A novel approach based on the trapping of tetracycline hydrochloride–loaded particles in polycaprolactone nanofibers was used to guide the regeneration processes of periodontal tissue at the gum interface. Chitosan nanoparticles loaded with different levels of tetracycline hydrochloride (up to 5% wt) were prepared by solution nebulization induced by electrical forces (i.e. electrospraying). The fine tuning of process parameters allows to obtain nanoparticles with tailored sizes ranging from 0.485 ± 0.147 μm to 0.639 ± 0.154 μm. The tetracycline hydrochloride release profile had a predominant burst effect for the first 70% of release followed by a relatively slow release over 24 h, which is promising for oral drug delivery. We also demonstrated that trapping tetracycline hydrochloride–loaded particles with submicrometer diameters into a polycaprolactone fiber network contributed to slowing the release of tetracycline hydrochloride from the nanoparticles, thus providing a more prolonged release in the periodontal pocket during clinical therapy. Preliminary studies on human mesenchymal stem cells confirm the viability of cells up to 5 days after culture, and thereby, validate the use of nanoparticle-/nanofiber-integrated systems in periodontal therapie

Ibuprofen-loaded poly(trimethylene carbonate-co-e-caprolactone) electrospun fibres for nerve regeneration

The development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well-known non-steroidal anti-inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate-co-e-caprolactone) [P(TMC-CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug-loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL) fibres. Under physiological conditions ibuprofen was released in 24h. The release process being diffusion-dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM-DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human-derived macrophages. The release of prostaglandin E 2 to the cell culture medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia in the framework of the project PEst-C/SAU/LA0002/2011 and PTDC/CTM-NAN/115124/2009, PTDC/SAU-ONC/112511/2009. L.R.P. thanks FCT for her PhD grant (SFRH /BD / 46015 / 2008) and M.J.O. is a FCT Ciência 200 7 fello w. The authors acknowledge Centro de Materiais da Universidade do Por to (C EMUP; RE EQ/1062/C TM/20 05 from FCT ) for t he 1HNMR analysis

Muon Energy Estimate Through Multiple Scattering with the Macro Detector

Muon energy measurement represents an important issue for any experiment addressing neutrino induced upgoing muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDC's included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for $E_\mu<$40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data.Comment: 25 pages, 11 figures, Submitted to Nucl. Instr. & Meth.

Low energy atmospheric muon neutrinos in MACRO

We present the measurement of two event samples induced by atmospheric $\nu_\mu$ of average energy $\bar {E}_\nu \sim 4 GeV$. In the first sample, the neutrino interacts inside the MACRO detector producing an upward-going muon leaving the apparatus. The ratio of the number of observed to expected events is $0.57 \pm0.05_{stat} \pm0.06_{syst} \pm0.14_{theor}$ with an angular distribution similar to that expected from the Bartol atmospheric neutrino flux. The second is a mixed sample of internally produced downward-going muons and externally produced upward-going muons stopping inside the detector. These two subsamples are selected by topological criteria; the lack of timing information makes it impossible to distinguish stopping from downgoing muons. The ratio of the number of observed to expected events is $0.71 \pm 0.05_{stat} \pm0.07_{syst} \pm0.18_{theor}$ . Using the ratio of the two subsamples (for which most theoretical uncertainties cancel) we can test the pathlength dependence of the oscillation hypothesis. The probability of agreement with the no-oscillation hypothesis is 5% . The deviations of our observations from the expectations has a preferred interpretation in terms of $\nu_\mu$ oscillations with maximal mixing and $\Delta m^2 \sim 10^{-3} \div 10^{-2} eV^2$. These parameters are in agreement with our results from upward throughgoing muons, induced by $\nu_\mu$ of much higher energies.Comment: 7 pages, 6 figures. Submitted to Phys. Lett.

Search for diffuse neutrino flux from astrophysical sources with MACRO

Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high energy upward-going muons among the sample of data collected by MACRO during ~5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 10^(-14) cm^(-2) s^(-1) sr^(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments.Comment: 19 pages, 8 figures, 2 table

Neutrino astronomy with the MACRO detector

High energy gamma ray astronomy is now a well established field and several sources have been discovered in the region from a few GeV up to several TeV. If sources involving hadronic processes exist, the production of photons would be accompanied by neutrinos too. Other possible neutrino sources could be related to the annihilation of WIMPs at the center of galaxies with black holes. We present the results of a search for point-like sources using 1100 upward-going muons produced by neutrino interactions in the rock below and inside the MACRO detector in the underground Gran Sasso Laboratory. These data show no evidence for a possible neutrino point-like source or for possible correlations between gamma ray bursts and neutrinos. They have been used to set flux upper limits for candidate point-like sources which are in the range 10^-14-10^-15 cm-2 s-1.Comment: 37 pages, 15 figures, replacement due to a typo in tab. 6, AASLaTex, submitted to Ap

Limits on dark matter WIMPs using upward-going muons in the MACRO detector

We perform an indirect search for Weakly Interacting Massive Particles (WIMPs) using the MACRO detector to look for neutrino-induced upward-going muons resulting from the annihilation of WIMPs trapped in the Sun and Earth. The search is conducted in various angular cones centered on the Sun and Earth to accommodate a range of WIMP masses. No significant excess over the background from atmospheric neutrinos is seen and limits are placed on the upward-going muon fluxes from Sun and Earth. These limits are used to constrain neutralino particle parameters from supersymmetric theory, including those suggested by recent results from DAMA/NaI.Comment: 14 pages, 7 figures, submitted to Phys. Rev.

Measurement of the residual energy of muons in the Gran Sasso underground Laboratories

The MACRO detector was located in the Hall B of the Gran Sasso underground Laboratories under an average rock overburden of 3700 hg/cm^2. A transition radiation detector composed of three identical modules, covering a total horizontal area of 36 m^2, was installed inside the empty upper part of the detector in order to measure the residual energy of muons. This paper presents the measurement of the residual energy of single and double muons crossing the apparatus. Our data show that double muons are more energetic than single ones. This measurement is performed over a standard rock depth range from 3000 to 6500 hg/cm^2.Comment: 28 pages, 9 figure

Observation of the Shadowing of Cosmic Rays by the Moon using a Deep Underground Detector

Using data collected by the MACRO experiment during the years 1989-1996, we show evidence for the shadow of the moon in the underground cosmic ray flux with a significance of 3.6 sigma. This detection of the shadowing effect is the first by an underground detector. A maximum-likelihood analysis is used to determine that the angular resolution of the apparatus is 0.9+/-0.3 degrees. These results demonstrate MACRO's capabilities as a muon telescope by confirming its absolute pointing ability and quantifying its angular resolution.Comment: 14 pages, 8 figures Submitted to Phys. Rev.

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic