A New Application of Lipid Nanoemulsions as Coating Agent, Providing Zero-Order Hydrophilic Drug Release from Tablets

The objective of the present investigation was to evaluate potential of nanoemulsions as a coating material for the tablets. The nanoemulsion of size less than 100 nm was prepared using a simple and low-energy spontaneous emulsification method. Conventional tablets containing theophylline as a model hydrophilic drug were prepared. The theophylline tablets were coated with the nanoemulsion using a fluid bed coater. The effect of different levels of the nanoemulsion coating on the theophylline release was evaluated. The theophylline tablets containing different levels of the nanoemulsion coating could be successfully prepared. Interestingly, the coating of tablet with the nanoemulsion resulted in zero-order release of theophylline from the tablets. The noncoated theophylline tablets release the entire drug in less than 2 minutes, whereas nanoemulsion coating delayed the release of theophylline from tablets. This investigation establishes the proof of concept for the potential of nanoemulsions as a coating material for tablets

Quantification of the volumetric benefit of image-guided radiotherapy (IGRT) in prostate cancer: margins and presence probability map

International audiencePURPOSE: To quantify the prostate and seminal vesicles (SV) anatomic variations in order to choose appropriate margins including intrapelvic anatomic variations. To quantify volumetric benefit of image-guided radiotherapy (IGRT). PATIENTS AND METHODS: Twenty patients, receiving a total dose of 70 Gy in the prostate, had a planning CT scan and eight weekly CT scans during treatment. Prostate and SV were manually contoured. Each weekly CT scan was registered to the planning CT scan according to three modalities: radiopaque skin marks, pelvis bone or prostate. For each patient, prostate and SV displacements were quantified. 3D maps of prostate and SV presence probability were established. Volumes including minimal presence probabilities were compared between the three modalities of registration. RESULTS: For the prostate intrapelvic displacements, systematic and random variations and maximal displacements for the entire population were: 5mm, 2.7 mm and 16.5mm in anteroposterior axis; 2.7 mm, 2.4mm and 11.4mm in superoinferior axis and 0.5mm, 0.8mm and 3.3mm laterally. Margins according to van Herk recipe (to cover the prostate for 90% of the patients with the 95% isodose) were: 8mm, 8.3mm and 1.9 mm, respectively. The 100% prostate presence probability volumes correspond to 37%, 50% and 61% according to the registration modality. For the SV, these volumes correspond to 8%, 14% and 18% of the SV volume. CONCLUSIONS: Without IGRT, 5mm prostate posterior margins are insufficient and should be at least 8mm, to account for intrapelvic anatomic variations. Prostate registration almost doubles the 100% presence probability volume compared to skin registration. Deformation of SV will require either to increase dramatically margins (simple) or new planning (not realistic)

Cavitation-induced force transition in confined viscous liquids under traction

We perform traction experiments on simple liquids highly confined between parallel plates. At small separation rates, we observe a simple response corresponding to a convergent Poiseuille flow. Dramatic changes in the force response occur at high separation rates, with the appearance of a force plateau followed by an abrupt drop. By direct observation in the course of the experiment, we show that cavitation accounts for these features which are reminiscent of the utmost complex behavior of adhesive films under traction. Surprisingly enough, this is observed here in purely viscous fluids.Comment: Submitted to Physical Review Letters on May 31, 2002. Related informations on http://www.crpp.u-bordeaux.fr/tack.htm

Overview of the predictive value of quantitative 18 FDG PET in head and neck cancer treated with chemoradiotherapy.

18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) allows to quantify the metabolic activity of a tumor (glycolysis) and has become a reference tool in oncology for the staging, restaging, radiotherapy planning and monitoring response in many cancers. Quantitative analyses have been introduced in order to overcome some of the limits of the visual methods, allowing an easier and more objective comparison of the inter- and intra-patients variations. The aims of this review were to report available evidences on the clinical value of quantitative PET/CT parameters in HNC. Forty-five studies, for a total of 2928 patients, were analyzed. Most of the data available dealt with the intensity of the metabolism, calculated from the Standard Uptake Value (SUV). Metabolic Tumor Volume (MTV) was well correlated with overall survival and disease free survival, with a higher predictive value than the maximum SUV. Spatial distribution of metabolism and textural analyses seems promising

Nematic-Wetted Colloids in the Isotropic Phase: Pairwise Interaction, Biaxiality and Defects

We calculate the interaction between two spherical colloidal particles embedded in the isotropic phase of a nematogenic liquid. The surface of the particles induces wetting nematic coronas that mediate an elastic interaction. In the weak wetting regime, we obtain exact results for the interaction energy and the texture, showing that defects and biaxiality arise, although they are not topologically required. We evidence rich behaviors, including the possibility of reversible colloidal aggregation and dispersion. Complex anisotropic self-assembled phases might be formed in dense suspensions.Comment: 4 pages, 6 figure

Salivary gland-sparing other than parotid-sparing in definitive head-and-neck intensity-modulated radiotherapy does not seem to jeopardize local control.

International audienceBACKGROUND: The objective was to analyze locoregional (LR) failure patterns in patients with head-and-neck cancer (HNC) treated using intensity-modulated radiotherapy (IMRT) with whole salivary gland-sparing: parotid (PG), submandibular (SMG), and accessory salivary glands represented by the oral cavity (OC). METHODS: Seventy consecutive patients with Stage I-II (23%) or III/IV (77%) HNC treated by definitive IMRT were included. For all LR failure patients, the FDG-PET and CT scans documenting recurrence were rigidly registered to the initial treatment planning CT. Failure volumes (Vf) were delineated based on clinical, radiological, and histological data. The percentage of Vf covered by 95% of the prescription isodose (Vf-V95) was analyzed. Failures were classified as "in-field" if Vf--V95 >= 95%, "marginal" if 20% < Vf-V95 < 95%, and "out-of-field" if Vf-V95 <=20%. Correlation between Vf-V95 and mean doses (Dmean) in the PG, SMG, and OC was assessed using Spearman's rank-order correlation test. The salivary gland dose impact on the LR recurrence risk was assessed by Cox analysis. RESULTS: The median follow-up was 20 months (6--35). Contralateral and ipsilateral PGs were spared in 98% and 54% of patients, respectively, and contralateral and ipsilateral SMG in 26% and 7%, respectively. The OC was spared to a dose <=40 Gy in 26 patients (37%). The 2-year LR control rate was 76.5%. One recurrence was "marginal", and 12 were "in-field". No recurrence was observed in vicinity of spared structures. Vf-V95 was not significantly correlated with Dmean in PG, SMG, and OC. The LR recurrence risk was not increased by lower Dmean in the salivary glands, but by T (p = 0.04) and N stages (p = 0.03). CONCLUSION: Over 92% of LR failures occurred "in-field" within the high dose region when using IMRT with a whole salivary gland-sparing strategy. Sparing SMG and OC in addition to PG thus appears a safe strategy

Selective sparing of bladder and rectum sub-regions in radiotherapy of prostate cancer combining knowledge-based automatic planning and multicriteria optimization

Background and Purpose: The association between dose to selected bladder and rectum symptom-related sub- regions (SRS) and late toxicity after prostate cancer radiotherapy has been evidenced by voxel-wise analyses. The aim of the current study was to explore the feasibility of combining knowledge-based (KB) and multi-criteria optimization (MCO) to spare SRSs without compromising planning target volume (PTV) dose delivery, including pelvic-node irradiation. Materials and Methods: Forty-five previously treated patients (74.2 Gy/28fr) were selected and SRSs (in the bladder, associated with late dysuria/hematuria/retention; in the rectum, associated with bleeding) were generated using deformable registration. A KB model was used to obtain clinically suitable plans (KB-plan). KB- plans were further optimized using MCO, aiming to reduce dose to the SRSs while safeguarding target dose coverage, homogeneity and avoiding worsening dose volume histograms of the whole bladder, rectum and other organs at risk. The resulting MCO-generated plans were examined to identify the best-compromise plan (KB + MCO-plan). Results: The mean SRS dose decreased in almost all patients for each SRS. D1% also decreased in the large majority, less frequently for dysuria/bleeding SRS. Mean differences were statistically significant (p < 0.05) and ranged between 1.3 and 2.2 Gy with maximum reduction of mean dose up to 3&#8211;5 Gy for the four SRSs. The better sparing of SRSs was obtained without compromising PTVs coverage. Conclusions: Selectively sparing SRSs without compromising PTV coverage is feasible and has the potential to reduce toxicities in prostate cancer radiotherapy. Further investigation to better quantify the expected risk reduction of late toxicities is warranted.This work has been supported by Fondazione Regionale per la Ricerca Biomedica, project nr. 110 - JTC PerPlanRT ERA PerMed, GA 779282.Publicad

Is a 3-mm intrafractional margin sufficient for daily image-guided intensity-modulated radiation therapy of prostate cancer?

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p\u3c0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p\u3c0.001). Of the 46 patients, three patients\u27 prostates and eight patients\u27 SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p\u3c0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage