Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.
A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0–2 Gy for carbon ions and 0–7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/gFe3o4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.
Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided.
1 January 2018 in Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
Quality assurance procedures required in modern radiotherapy would greatly benefit from the development of tissue equivalent dosimeters able to render three-dimensional dose profiles with a high spatial resolution. In this scenario, Fricke gel (FG) dosimeters could be good candidates, but some limitations have restricted their use in clinical practice. Recently, formulations based on gel matrices of poly(vinyl-alcohol) (PVA) chemically cross-linked with glutaraldehyde (GTA) have shown improvements compared to FGs with natural matrices. The purpose of this study is the characterization of the dosimetric properties of radiochromic PVA–GTA FG dosimeters by means of absorption spectroscopy measurements. Xylenol orange (XO) FG dosimeters, prepared in spectrophotometry cuvettes using 9.1 w/w of Mowiol ® -PVA and 26.5 mM of GTA, were uniformly irradiated with a 137 Cs source and with 6 and 15 MV x-rays generated by a medical linear accelerator. Ultraviolet–visible absorbance spectra collected at consecutive times post-irradiation showed that a time of approximately 15 min is sufficient to reach a stable absorbance value, indicating the achievement of a chemical equilibrium in the complexation processes between Fe 3+ and XO. The analysis of the change of the absorbance spectra shape with the cumulated dose demonstrated that a linear dose–response curve of PVA–GTA FG dosimeters is obtained in the entire investigated dose interval of 0.5–15 Gy by properly choosing the wavelength used for the absorbance measurements. Furthermore, PVA–GTA FG dosimeters proved to be nearly water- and tissue-equivalent and characterized by a response independent of the energies and dose rates in the investigated intervals. These findings suggested that PVA–GTA FGs are promising tools for dosimetry applications in external x-ray radiation therapy.
Over the years, many efforts have been made to develop radiation detectors to handle the complex issues of small field dosimetry and achieve the increasing accuracy, precision and in vivo dose monitoring required by the new advanced treatment modalities. In this context, interest has surged in the development of sensors based on scintillating optical fibres. In this paper, the near-infrared radioluminescence and dosimetric properties of Yb-doped silica optical fibres, coupled with a laboratory prototype based on an avalanche photodiode, were studied by irradiating the fibres with photons and electron beams generated by a Varian Trilogy accelerator. The performance of the system in standard and small field sizes has also been investigated, comparing the output factor, percentage depth dose and off-axis ratio measurements of the prototypal detector with other commercial sensors, including the Exradin W1 scintillator. The results of this study demonstrate that the drawback due to the stem effect in Yb-doped silica optical fibres can be managed in a simple but effective way by optical filtering. The robustness of the system in complex dosimetric scenarios and the accuracy and precision achieved by Yb-doped fibres in relative dose assessments suggest an effective use of the system for real-time in vivo dosimetry applications.