Dataset Information

Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.

ABSTRACT: PURPOSE:The purpose of this study is to investigate a sol-gel transition property and content release profiles for thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogels carrying paclitaxel, rapamycin, and LS301, and to present a proof-of-concept that PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, called TheranoGel, exhibit excellent theranostic activity in peritoneal ES-2-luc ovarian cancer xenograft mice. METHODS:Thermosensitive PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, individually or in combination, were prepared via a lyophilization method, characterized with content release kinetics, and assessed with theranostic activity in ES-2-luc xenograft mice. RESULTS:A thermosensitive PLGA-b-PEG-b-PLGA sol-gel system was able to entrain 3 poorly water-soluble payloads, paclitaxel, rapamycin, and LS301 (TheranoGel). TheranoGel made a sol-to-gel transition at 37°C and slowly released 3 drugs at a simultaneous release rate in response to the physical dissociation of hydrogels in vitro. TheranoGel enabled loco-regional delivery of multi-drugs by forming a gel-depot in the peritoneal cavity of ES-2-luc xenograft mice. An intraperitoneal (IP) administration of TheranoGel resulted in excellent therapeutic and diagnostic activities, leading to the improved peritoneal surgery in ES-2-luc xenograft mice. CONCLUSIONS:TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo.

SUBMITTER: McKenzie M

PROVIDER: S-EPMC7335463 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.

McKenzie Matthew M Betts David D Suh Amy A Bui Kathryn K Tang Rui R Liang Kexian K Achilefu Samuel S Kwon Glen S GS Cho Hyunah H

Pharmaceutical research 20160609 9

<h4>Purpose</h4>The purpose of this study is to investigate a sol-gel transition property and content release profiles for thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogels carrying paclitaxel, rapamycin, and LS301, and to present a proof-of-concept that PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, called TheranoGel, exhibit excellent theranostic activity in peritoneal ES-2-lu ...[more]

PMID: 27283829

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Project description:The purpose of this article is to present the first imaging experiments to demonstrate the functional equivalence between a conventional rotational gantry and a fixed-beam imaging geometry, and the feasibility of an iterative image-reconstruction technique under gravitational deformation.Experiments were performed using an Elekta Axesse with Agility MLC and XVI, a custom-built rotating phantom stage, a Catphan QA phantom, and a porcine heart. For the imaging equivalence, a conventional cone beam computed tomography (CBCT) of the Catphan was acquired, as well as a set of 660 x-ray projections with a static gantry and rotating Catphan. Both datasets were reconstructed with the Feldkamp-Davis-Kress (FDK) algorithm, and the resultant volumetric images were compared using standard metrics. For imaging under gravitational deformation, a conventional CBCT of the Catphan and a set of 660 x-ray projections with a static gantry and rotating Catphan were also acquired with a porcine heart. The conventional CBCT was reconstructed using FDK. The projections that were acquired with the heart rotating were sorted into angular bins and reconstructed with prior image constrained compressed sensing using a deformation-blurred FDK prior. Deformation was quantified with B-spline transformation-based deformable image registration.For imaging equivalence, the difference between the two Catphan images was consistent with Poisson noise. For imaging under gravitational deformation, the conventional CBCT porcine heart image (ground truth at 0 degrees) matched the static gantry, rotating heart reconstruction with a mean magnitude of <3 mm and maximum magnitude of <5 mm of the deformation vector field. The mean deformation of the rotating heart was 3.0 to 8.9 mm, up to 16.1 mm maximum deformation. Deformation was mainly observed in the direction of gravity.We have demonstrated imaging equivalence in cone beam CT reconstructions between rigid phantom images acquired with a conventional rotating gantry and with a fixed-gantry and rotating phantom. We have presented a method for image reconstruction under a fixed-beam imaging geometry using a deformable phantom.

Project description:The objective of this proof-of-concept study was to demonstrate the targeted delivery of erythropoietin (EPO) using magnetically guided magnetic nanoparticles (MNPs).MNPs consisting of a ferric-ferrous mixture (FeCl3·6H2O and FeCl2·4H2O) were prepared using a co-precipitation method. The drug delivery system (DDS) was manufactured via the spray-drying technique using a nanospray-dryer. The DDS comprised 7.5 mg sodium alginate, 150 mg MNPs, and 1000 IU EPO.Scanning electron microscopy revealed DDS particles no more than 500 nm in size. Tiny particles on the rough surfaces of the DDS particles were composed of MNPs and/or EPO, unlike the smooth surfaces of the only alginate particles. Transmission electron microscopy showed the tiny particles from 5 to 20 nm in diameter. Fourier-transform infrared spectroscopy revealed DDS peaks characteristic of MNPs as well as of alginate. Thermal gravimetric analysis presented that 50% of DDS weight was lost in a single step around 500°C. The mode size of the DDS particles was approximately 850 nm under in vivo conditions. Standard soft lithography was applied to DDS particles prepared with fluorescent beads using a microchannel fabricated to have one inlet and two outlets in a Y-shape. The fluorescent DDS particles reached only one outlet reservoir in the presence of a neodymium magnet. The neurotoxicity was evaluated by treating SH-SY5Y cells in 48-well plates (1 × 10 cells/well) with 2 μL of a solution containing sodium alginate (0.075 mg/mL), MNPs (1.5 mg/mL), or sodium alginate + MNPs. A cell viability assay kit was used to identify a 93% cell viability after MNP treatment and a 94% viability after sodium alginate + MNP treatment, compared with the control. As for the DDS particle neurotoxicity, a 95% cell viability was noticed after alginate-encapsulated MNPs treatment and a 93% cell viability after DDS treatment, compared with the control.The DDS-EPO construct developed here can be small under in vivo conditions enough to pass through the lung capillaries with showing the high coating efficiency. It can be guided using magnetic control without displaying significant neurotoxicity in the form of solution or particles.

Project description:AimsThe aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT).Methods and resultsIn a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] μg/mL vs. 1.6 [1.20-3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] μg/mL vs. 0.9 [0.45-2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups.ConclusionsIntraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.

Project description:PurposeAutomation and computer assistance can support quality assurance tasks in radiotherapy. Retrospective image review requires significant human resources, and automation of image review remains a noteworthy missing element in previous work. Here, we present initial findings from a proof-of-concept clinical implementation of an AI-assisted review of CBCT registrations used for patient setup.MethodsAn automated pipeline was developed and executed nightly, utilizing python scripts to interact with the clinical database through DICOM networking protocol and automate data retrieval and analysis. A previously developed artificial intelligence (AI) algorithm scored CBCT setup registrations based on misalignment likelihood, using a scale from 0 (most unlikely) through 1 (most likely). Over a 45-day period, 1357 pre-treatment CBCT registrations from 197 patients were retrieved and analyzed by the pipeline. Daily summary reports of the previous day's registrations were produced. Initial action levels targeted 10% of cases to highlight for in-depth physics review. A validation subset of 100 cases was scored by three independent observers to characterize AI-model performance.ResultsFollowing an ROC analysis, a global threshold for model predictions of 0.87 was determined, with a sensitivity of 100% and specificity of 82%. Inspecting the observer scores for the stratified validation dataset showed a statistically significant correlation between observer scores and model predictions.ConclusionIn this work, we describe the implementation of an automated AI-analysis pipeline for daily quantitative analysis of CBCT-guided patient setup registrations. The AI-model was validated against independent expert observers, and appropriate action levels were determined to minimize false positives without sacrificing sensitivity. Case studies demonstrate the potential benefits of such a pipeline to bolster quality and safety programs in radiotherapy. To the authors' knowledge, there are no previous works performing AI-assisted assessment of pre-treatment CBCT-based patient alignment.

Dataset Information

Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.

Publications

Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.

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