A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

An underground Sagnac gyroscope with sub-prad/s rotation rate sensitivity: toward General Relativity tests on Earth

Measuring in a single location on Earth its angular rotation rate with respect to the celestial frame, with a sensitivity enabling access to the tiny Lense-Thirring effect is an extremely challenging task. GINGERINO is a large frame ring laser gyroscope, operating free running and unattended inside the underground laboratory of the Gran Sasso, Italy. The main geodetic signals, i.e., Annual and Chandler wobbles, daily polar motion and Length of the Day, are recovered from GINGERINO data using standard linear regression methods, demonstrating a sensitivity better than 1 prad/s, therefore close to the requirements for an Earth-based Lense-Thirring test.Comment: 7 pages, 5 figure

Erratum to: Constraining theories of gravity by GINGER experiment

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GINGER - Toward an experimental test of General Relativity

GINGER (Gyroscopes IN General Relativity) is a proposal for measuringthe Lense-Thirring effect using an array of ring laser-gyroscopes. Those are,nowadays, the most sensitive inertial sensors to measure the rotation rateof the Earth.The Lense-Thirring contribution to the Earth gravitational field marks itself as a tinDC perturbation onto Ω Ω, the Earth rotation rate. Its magnitude is 10−9×Ω−9×Ω so that to be able to discriminate it a very high sensitivity andlong measurement times in order to move toward low frequency are required. For such an experiment, an undergroundlocation guarantees further isolation from anthropic as well as environmentaldisturbances.GINGERINO is a single axis ring laser located inside the theINFN Gran Sasso laboratory. It has demonstrated that the very high thermal stability of the cave allows continuous operation, and sensitivity well below fractions of nrad/s are feasible with duty cycle above 90% even without stabilisation of the scale factor of the ring laser.Here we show the GINGER experiment concept together with the first evaluation of the GINGERINO sensitiviy that shows how such a device can be of use also in earth science and related phenomena

Sensitivity limit investigation of a Sagnac gyroscope through linear regression analysis

The sensitivity to angular rotation of the top class Sagnac gyroscope GINGERINO is carefully investigated with standard statistical means, using 103 days of continuous operation and the available geodesic measurements of the Earth angular rotation rate. All features of the Earth rotation rate are correctly reproduced. The unprecedented sensitivity of fractions of frad/s is attained for long term runs. This excellent sensitivity and stability put Sagnac gyroscopes at the forefront for fundamental physics, in particular for tests of general relativity and Lorentz violation, where the sensitivity plays the key role to provide reliable data for deeper theoretical investigations

Deep underground rotation measurements: GINGERino ring laser gyroscope in Gran Sasso

GINGERino is a large frame laser gyroscope investigating the ground motion in the most inner part of the underground international laboratory of the Gran Sasso, in central Italy. It consists of a square ring laser with a 3.6 m side. Several days of continuous measurements have been collected, with the apparatus running unattended. The power spectral density in the seismic bandwidth is at the level of 10−10 (rad/s)/√Hz. A maximum resolution of 30 prad/s is obtained with an integration time of few hundred seconds. The ring laser routinely detects seismic rotations induced by both regional earthquakes and teleseisms. A broadband seismic station is installed on the same structure of the gyroscope. First analysis of the correlation between the rotational and the translational signal is presented

Constraining theories of gravity by GINGER experiment

The debate on gravity theories to extend or modify General Relativity is very active today because of the issues related to ultra-violet and infra-red behavior of Einstein's theory. In the first case, we have to address the Quantum Gravity problem. In the latter, dark matter and dark energy, governing the large scale structure and the cosmological evolution, seem to escape from any final fundamental theory and detection. The state of art is that, up to now, no final theory, capable of explaining gravitational interaction at any scale, has been formulated. In this perspective, many research efforts are devoted to test theories of gravity by space-based experiments. Here we propose straightforward tests by the GINGER experiment, which, being Earth based, requires little modeling of external perturbation, allowing a thorough analysis of the systematics, crucial for experiments where sensitivity breakthrough is required. Specifically, we want to show that it is possible to constrain parameters of gravity theories, like scalar-tensor or Horava-Lifshitz gravity, by considering their post-Newtonian limits matched with experimental data. In particular, we use the Lense-Thirring measurements provided by GINGER to find out relations among the parameters of theories and finally compare the results with those provided by LARES and Gravity Probe-B satellites.Comment: 15 pages, 3 figures, accepted for publication in EPJ