Vivo Testing Research Articles

Boroxazolidones: Synthesis, In Silico and In Vitro Evaluation as ACE/AChE Dual Inhibitors, and In Vivo Testing of Antihypertensive Activity.

Systemic arterial hypertension is a serious chronic health problem caused by multiple factors. It is a major risk factor for Cardiovascular Diseases (CVDs), including heart failure, coronary heart disease, and myocardial infarction. Hypertension can be effectively treated with inhibitors of the Angiotensin Converting Enzyme (ACE), such as captopril, enalapril, and lisinopril. However, these drugs are associated with significant adverse reactions (e.g., persistent coughing, skin rashes, and angioedema). Considering the recent insights obtained by our group into the antihypertensive effect of boroxazolidones, the aim of the current contribution was to design and synthesize a series of these compounds derived from α-amino acids and evaluate them (in silico and in vitro) as inhibitors of ACE and acetylcholinesterase (AChE). The best candidates were examined for their in vivo antihypertensive activity to regulate high blood pressure in male spontaneously hypertensive rats. Although boron-containing compounds were once thought to be toxic in any medical context, they have increasingly been used as antibiotics, antiseptics, and antineoplastic agents. BXZHis, BXZ-Lys, BXZ-Orn, BXZ-Phe, and BXZ-Pro were selected in silico as promising ACE and AChE inhibitors. After synthesis, these molecules were tested in vitro as ACE and AChE inhibitors, finding that most were effective at micromolar concentrations. The two best candidates, BXZ-Lys and BXZ-His, were evaluated in vivo with spontaneously hypertensive rats. BXZ-Lys significantly decreased systolic, diastolic, and mean blood pressure, being more potent than a common ACE inhibitor, captopril. Future research is required to elucidate the mechanism of action of this antihypertensive effect.

In Vivo Testing of a Second-Generation Prototype Accessory for Single Transapical Left Ventricular Assist Device Implantation.

A new accessory was developed to allow implantation of left ventricular assist devices (LVADs) without requiring an anastomosis to the ascending aorta. The accessory combines the LVAD inflow and outflow into a dual-lumen device. Initial prototypes encountered reduced pump performance in vitro, but a second-generation prototype successfully addressed this issue. This feasibility study aimed to demonstrate the anatomic fit, safe implantation, and hemodynamic effectiveness of the LVAD with the accessory. The accessory was implanted in ten female pigs (104 ± 13 kg). Following sternotomy and apical coring under cardiopulmonary bypass, a balloon catheter was retrogradely inserted and exteriorized through the coring site, where it was inflated within the distal third of the outflow graft. It was utilized to pull the accessory's outflow across the aortic valve. After LVAD attachment, the catheter was removed. Echocardiography revealed no relevant valve regurgitation post-implantation. During ramp testing, pump flow increased from 3.7 ± 1.2 to 5.4 ± 1.2 L/min. Necropsy confirmed correct accessory placement in nine animals. No valve lesions or device thrombosis were observed. The accessory enabled LVAD implantation without compromising pump performance. Future work includes design refinements for implantation without cardiopulmonary bypass and long-term testing in a chronic heart failure model.

Design, Development, and In Vivo Testing of the Hydrating Effect and pH Maintenance a Cosmetic Formulation Incorporating Oils and an Extract from Peruvian Biodiversity

Design, Development, and In Vivo Testing of the Hydrating Effect and pH Maintenance a Cosmetic Formulation Incorporating Oils and an Extract from Peruvian Biodiversity

Abstract LB402: In vivo efficacy of anti-B7-H3 antibody-drug conjugate (ADC) ifinatamab deruxtecan (I-DXd; DS-7300): An update from the Pediatric Preclinical In Vivo Testing (PIVOT) Program

Abstract Introduction: I-DXd (DS-7300) is a B7-H3-directed ADC with a topoisomerase 1 inhibitor payload (an exatecan derivative, DXd). I-DXd has demonstrated clinical efficacy in adults with heavily pretreated solid tumors (Patel et al., ESMO 2023). We previously reported that I-DXd induced objective responses in PDX models for multiple B7-H3 (CD276) expressing pediatric histologies, including rhabdomyosarcoma, osteosarcoma, neuroblastoma, and Wilms tumor. We extend these results with dose-response testing and include an isotype control ADC (IC-ADC) to evaluate whether B7-H3 expression is required for optimal response. Methods: PDX models were dosed with vehicle, I-DXd, or IC-ADC, the latter two at 1, 3, and 10 mg/kg intravenously on days 1 and 15. Testing was performed using 5 animals per treatment group. Activity was assessed by the PIVOT objective response measure (ORM) (Ped Blood Cancer 2007;49:928-940) that defines objective response as partial, complete, or maintained complete response (PR, CR, and MCR) compared to stable disease (SD) or progressive disease, with or without growth delay (PD2 and PD1, respectively). Results: I-DXd showed dose-dependent activity with MCR for all 5 models at 10 mg/kg. PR or MCR responses were observed in 4 of 5 models to I-DXd at 3 mg/kg, with no objective responses to I-DXd at 1 mg/kg. Only the RMS model showed objective response to IC-ADC. For all models I-DXd was significantly more active than IC-ADC. Conclusions: We confirm significant anti-tumor activity for I-DXd for multiple pediatric solid tumors with B7-H3 expression and provide evidence of a dose response effect for I-DXd and for enhanced efficacy for I-DXd versus IC-ADC. Testing in additional preclinical models (neuroblastoma and glioblastoma) is underway. Due to the uniform high expression of B7-H3 in multiple pediatric histologies, I-DXd warrants evaluation for clinical activity in pediatric solid tumor patients. TABLE 1. NAND Activity for DS-7300a and Isotype Control using the PIVOT Objective Response Measure (ORM) Line IHC B7-H3 H-Score Diagnosis DS-7300a Isotype Control 1 mg/kg 3 mg/kg 10 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg OS-9 230 Osteosarcoma PD2 PR MCR PD1 PD1 PD1 OS-33 240 Osteosarcoma PD2 MCR MCR PD1 PD2 SD Rh30 140 Rhabdomyosarcoma PD2 MCR MCR PD1 PR MCR WT11 150 Wilms tumor PD1 PD2 MCR PD1 PD1 PD1 Felix 210 Neuroblastoma PD2 MCR MCR PD1 PD1 PD2 Citation Format: Richard Gorlick, Jonathan Gill, Wendong Zhang, Yael Mosse, John Maris, David Groff, Malcolm Smith, Beverly Teicher, Steve Neuhauser, Tim Stearns, Vivek Philip, Emily Jocoy, Jeff Chuang, Carol J. Bult, Jun Hasegawa, Xiaozhong Qian, Peter Houghton, Raushan Kurmasheva. In vivo efficacy of anti-B7-H3 antibody-drug conjugate (ADC) ifinatamab deruxtecan (I-DXd; DS-7300): An update from the Pediatric Preclinical In Vivo Testing (PIVOT) Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB402.

Abstract 5468: Pediatric Preclinical In Vivo Testing (PIVOT) data portal enables access to 15 years of retrospective treatment study data in support of prospective study design

Abstract The PIVOT program (https://preclinicalpivot.org) is a National Cancer Institute (NCI) funded initiative in support of the RACE Act that funds collaborations between academic centers and industry partners to test the efficacy of targeted cancer treatments developed for adult oncology for potential application in diverse pediatric cancers, including cancers of the central nervous system, leukemia, osteosarcoma, sarcoma, and neuroblastoma. In support of the PIVOT program, we have harmonized more than 15 years of data collected during two previous preclinical pediatric testing programs. To disseminate the data and results of these programs broadly we designed and implemented the PIVOT Data Portal. The PIVOT Data Portal is an R Shiny App that makes treatment efficacy data from PIVOT accessible on the web. The data are harmonized which supports comparison of treatment results across different cancer types. The data from the portal are freely available and downloadable. The portal includes study summaries within and across cancer models, statistical reports, tables, and tools for the visualization of treatment results. Data summary tables include entries for objective response measures (ORM), mean outcome, number of tumor studies, and p-value as appropriate. Visualizations include relative tumor volume plots for solid tumors; CD45 plots for leukemia; and survival curves to compare survival time across treatment groups. Treatment study visualizations and data summaries with their related metadata can be generated and downloaded within the Shiny App, allowing researchers to perform further downstream analysis. The portal collectively contains data for 52 agents, 45 drug targets, 34 drug classes (including ADCs, small molecular inhibitors, protein degraders, BiTEs, etc.), and 167 models, with a total of 245,926 data points. Currently, 44% of agents have been tested on 2 or more cancer types. Among the solid tumor models tested, 10 had at least one treatment that resulted in an ORM of maintained complete response (MCR), while 29 leukemia models had an ORM of MCR. Similarly, 48% of agents tested had an ORM of MCR for at least one cancer type. The PIVOT Data Portal makes pediatric cancer model treatment data available without restriction to support retrospective analyses and design of prospective studies. We are working to link cancer model data within the portal to molecular data. Merging outcome data with genomics data will facilitate computational approaches for molecular target identification, personalized treatment, and treatment optimization. Citation Format: Saul E. Acevedo, Tim M. Stearns, Phillip Webster, Vivek Philip, Michael W. Lloyd, Anuj Srivastava, Steven Neuhauser, Dale Begley, Debbie Krupke, Emily L. Jocoy, Carol J. Bult, Jeffrey H. Chuang, Dennis A. Dean. Pediatric Preclinical In Vivo Testing (PIVOT) data portal enables access to 15 years of retrospective treatment study data in support of prospective study design [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5468.

In Vivo Testing of an Ambient Air Based, Portable, and Automated CO 2 Removal Controller for Artificial Lungs.

Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications.

Polyacrylamide Hydrogel Containing Calendula Extract as a Wound Healing Bandage: In Vivo Test.

Hydrogel is a biomaterial widely used in several areas of industry due to its great biocompatibility and adaptability to biological tissues. In Brazil, the Calendula plant is approved by the Ministry of Health as a medicinal herb. It was chosen to be incorporated in the hydrogel formulation because of its anti-inflammatory, antiseptic and healing effects. This study synthesized polyacrylamide hydrogel containing calendula extract and evaluated its efficiency as a bandage for wound healing. The hydrogels were prepared using free radical polymerization and characterized by Scanning Electron Microscopy, swelling analysis and mechanical properties by texturometer. The morphology of the matrices showed large pores and foliaceous structure. In vivo testing, as well as the evaluation of acute dermal toxicity, was conducted using male Wistar rats. The tests indicated efficient collagen fiber production, improved skin repair and no signs of dermal toxicity. Thus, the hydrogel presents compatible properties for the controlled release of calendula extract used as a bandage to promote cicatrization.

Tadalafil-Loaded Self-Nanoemulsifying Chewable Tablets for Improved Bioavailability: Design, In Vitro, and In Vivo Testing.

This research aimed to develop innovative self-nanoemulsifying chewable tablets (SNECT) to increase oral bioavailability of tadalafil (TDL), a nearly insoluble phosphodiesterase-5 inhibitor. Cinnamon essential oil, PEG 40 hydrogenated castor oil (Cremophor® RH 40), and polyethylene glycol 400 served as the oil, surfactant, and cosurfactant in the nanoemulsifying system, respectively. Primary liquid self-nanoemulsifying delivery systems (L-SNEDDS) were designed using phase diagrams and tested for dispersibility, droplet size, self-emulsifying capability, and thermodynamic stability. Adsorption on a carrier mix of silicon dioxide and microcrystalline cellulose was exploited to solidify the optimum L-SNEDDS formulation as self-nanoemulsifying granules (SNEG). Lack of crystalline TDL within the granules was verified by DSC and XRPD. SNEG were able to create a nanoemulsion instantaneously (165 nm), a little larger than the original nanoemulsion (159 nm). SNECT were fabricated by compressing SNEG with appropriate excipients. The obtained SNECT retained their quick dispersibility dissolving 84% of TDL within 30 min compared to only 18% dissolution from tablets of unprocessed TDL. A pharmacokinetic study in Sprague–Dawley rats showed a significant increase in Cmax (2.3-fold) and AUC0–24 h (5.33-fold) of SNECT relative to the unprocessed TDL-tablet (p < 0.05). The stability of TDL-SNECT was checked against dilutions with simulated GI fluids. In addition, accelerated stability tests were performed for three months at 40 ± 2 °C and 75% relative humidity. Results revealed the absence of obvious changes in size, PDI, or other tablet parameters before and after testing. In conclusion, current findings illustrated effectiveness of SNECT to enhance TDL dissolution and bioavailability in addition to facilitating dose administration.

Poster 105: Nanowarming by Inductive Heating of Vitrified Large Articular Cartilage Specimens, In Vivo Testing with Hanford Mini Pigs

Poster 105: Nanowarming by Inductive Heating of Vitrified Large Articular Cartilage Specimens, In Vivo Testing with Hanford Mini Pigs

BIO2: Acute In Vivo Testing of a Portable Controller to Automate CO2 Removal in Artificial Lungs

BIO2: Acute In Vivo Testing of a Portable Controller to Automate CO2 Removal in Artificial Lungs

MP14-04 IN VIVO AND BENCH TESTING OF A CONCEPT SINGLE USE URETEROSCOPE BSC COMPARED TO REFERENCE SINGLE USE AND REUSABLE URETEROSCOPES

You have accessJournal of UrologyCME1 May 2022MP14-04 IN VIVO AND BENCH TESTING OF A CONCEPT SINGLE USE URETEROSCOPE BSC COMPARED TO REFERENCE SINGLE USE AND REUSABLE URETEROSCOPES Naeem Bhojani, Nabil Shalabi, K. F. Victor Wong, Roman Herout, Alina Reicherz, and Ben H. Chew Naeem BhojaniNaeem Bhojani More articles by this author , Nabil ShalabiNabil Shalabi More articles by this author , K. F. Victor WongK. F. Victor Wong More articles by this author , Roman HeroutRoman Herout More articles by this author , Alina ReicherzAlina Reicherz More articles by this author , and Ben H. ChewBen H. Chew More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002543.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The introduction of the first single use ureteroscope over 5 years ago established a new paradigm in the surgical management of kidney stone disease and since then several new single use ureteroscopes have been developed. Furthermore, improvements in chip technology, resolution and maneuverability have been employed in this newer generation of single use ureteroscopes. This study sought to objectively test if a concept single use ureteroscope (Boston Scientific, USA, concept device, not available for sale) with pressure monitoring technology is able to achieve comparable optical performance and maneuverability as reference single use and reusable ureteroscopes. METHODS: We bench tested 3 single-use ureteroscopes, 1 reusable ureteroscope and the new concept Boston Scientific single-use ureteroscope with pressure monitoring technology. All scopes were brand new. Optical characteristics as well as manoeuverability were compared. Resolution was measured using a 1951 USAF 3x3 inch, positive Resolution Target at distances of 10mm, 20mm and 30mm using 5 different solutions. Field of view was measured. Manoeuverability and visualization was measured in cadaveric kidneys and 2 anesthetized farm pigs. Finally, pressure studies using a pressure sensing calibrator (ElveFlow OB1 Pressure Controller) was used to determine accuracy of the BSC concept device. RESULTS: The 365 micron laser fiber significantly decreased deflection for all scopes (Fig 1) and resolution significantly decreased for most scopes with increasing distance (Fig 2). Field of view of the BSC concept scope was found to be wider than all other scopes (Fig 3). Manoeuverability of scopes was found to be comparable. Notably, pressure readings from the concept scope and the pressure sensing calibrator strongly corelated with each other (r=0.9983) (Fig 4). CONCLUSIONS: In this non-clinical study, concept ureteroscope with pressure monitoring technology was found to achieve comparable optical performance and maneuverability as the reference single use and reusable ureteroscopes. In regard to the pressure measurement capability, the readings from the concept single use flexible ureteroscope were comparable to the pressure sensing calibrator. Source of Funding: This work was supported by Boston Scientific Inc © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e232 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naeem Bhojani More articles by this author Nabil Shalabi More articles by this author K. F. Victor Wong More articles by this author Roman Herout More articles by this author Alina Reicherz More articles by this author Ben H. Chew More articles by this author Expand All Advertisement PDF DownloadLoading ...

In Vivo Testing of Coated Nanoparticles as Medication Delivery and Liver Integrity Monitoring in Mice's

The study's goal is to assay the effect of using therapeutic nanoparticles on the liver. The study involves the estimation of aminotransferase ALT, AST and alkaline phosphate ALP levels in patients before and after using nanoparticles. Gold nanoparticles (Gnps) were created using a chemical method, then coated with polyethylene glycol (Peg), followed by Ultra violet spectrophotometry, transmission electron microscopy (TEM), and surface charge studies to determine their sizes, then were investigate the effect of using therapeutic nanoparticles on the liver. The results show that before coating with Peg, the size of Gnps was 22.65 and 23.82 nm, while after coating with Peg, the size of Gnps was 76.50 and 80.15 nm. The maximum absorption was at 515.5 nm and became 530.5 nm when using UV, and it was -29.65 and became -9.4 when using zeta potential, experiments are ongoing for (60) days. The result revealed that the liver enzymes (AST and ALT) has a significant effect when injecting Gnps. While the effect was less on both liver enzymes (AST and ALT) when injecting Gnps + Peg.

Amorphous Solid Dispersions and the Contribution of Nanoparticles to In Vitro Dissolution and In Vivo Testing: Niclosamide as a Case Study.

We developed an amorphous solid dispersion (ASD) of the poorly water-soluble molecule niclosamide that achieved a more than two-fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60-fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, Biopharmaceutics Classification System (BCS) class II, and a poor glass former with low bioavailability in vivo. Hot-melt extrusion is a high-throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP–VA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and dynamic light scattering (DLS). The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side-by-side diffusion test, these nanoparticles produced a four-fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

Multi-Modal PET and MR Imaging in the Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM) Model for Initial In Vivo Testing of Target-Specific Radioligands

The validation of novel target-specific radioligands requires animal experiments mostly using mice with xenografts. A pre-selection based on a simpler in vivo model would allow to reduce the number of animal experiments, in accordance with the 3Rs principles (reduction, replacement, refinement). In this respect, the chick embryo or hen’s egg test–chorioallantoic membrane (HET-CAM) model is of special interest, as it is not considered an animal until day 17. Thus, we evaluated the feasibility of quantitative analysis of target-specific radiotracer accumulation in xenografts using the HET-CAM model and combined positron emission tomography (PET) and magnetic resonance imaging (MRI). For proof-of-principle we used established prostate-specific membrane antigen (PSMA)-positive and PSMA-negative prostate cancer xenografts and the clinically widely used PSMA-specific PET-tracer [68Ga]Ga-PSMA-11. Tracer accumulation was quantified by PET and tumor volumes measured with MRI (n = 42). Moreover, gamma-counter analysis of radiotracer accumulation was done ex-vivo. A three- to five-fold higher ligand accumulation in the PSMA-positive tumors compared to the PSMA-negative tumors was demonstrated. This proof-of-principle study shows the general feasibility of the HET-CAM xenograft model for target-specific imaging with PET and MRI. The ultimate value for characterization of novel target-specific radioligands now has to be validated in comparison to mouse xenograft experiments.

Best Practices for Preclinical In Vivo Testing of Cancer Nanomedicines.

Significant advances have been made in the development of nanoparticles for cancer treatment in recent years. Despite promising results in preclinical animal models, cancer nanomedicines often fail in clinical trials. This failure rate could be reduced by defining stringent criteria for testing and quality control during the design and development stages, and by performing carefully planned preclinical studies in relevant animal models. This article discusses best practices for the evaluation of nanomedicines in murine tumor models. First, a recommended set of experiments to perform is introduced, including discussion of the types of data to collect during these studies. This is followed by an outline of various tumor models and their clinical relevance. Next, different routes of nanoparticle administration are overviewed, followed by a summary of important controls to include in in vivo studies of nanomedicine. Finally, animal welfare considerations are discussed, and an overview of the steps involved in achieving US Food and Drug Administration approval after animal studies are completed is provided. Researchers should use this report as a guideline for effective preclinical evaluation of cancer nanomedicine. As the community adopts best practices for in vivo testing, the rate of clinical translation of cancer nanomedicines is likely to improve.

Rhenium-Based Complexes and in Vivo Testing: A Brief History.

The success of metal‐based anticancer therapeutics in the treatment of cancer is best exemplified by cisplatin. Currently used in 32/78 cancer regimens, metal‐based drugs have a clear role in cancer therapy. Despite this, metal‐based anticancer therapeutics are not without drawbacks, with issues such as toxic side effects and the development of resistance mechanisms. This has led to investigations of other metal‐based drug candidates such as auranofin, a gold‐based drug candidate as well as ruthenium‐based candidates, NAMI‐A, NKP‐1339 and TLD‐1433. All are currently undergoing clinical trials. Another class of complexes under study are rhenium‐based; such complexes have undergone extensive in vitro testing but only nine have been reported to display antitumour in vivo activity, which is a necessary step before entering clinical trials. This review will document, chronologically, the rhenium‐based drug candidates that have undergone in vivo testing and the outlook for such complexes.

In Vivo Testing and Extended Drug Release of Chitosan-Coated Itraconazole Loaded Microemulsion Using Volatile Oil Thymus vulgaris

Microemulsions are potent drug delivery vehicles as they solubilize water insoluble drugs with poor bioavailability. The main aim of this study was to develop, optimize, and assess a thyme oil microemulsion with inherent antifungal activity for transdermal drug delivery of itraconazole. The optimized thyme oil microemulsion contains thyme oil, Cremophor EL, and water at 5:25:70% v/v respectively. The drug loaded microemulsion was mixed in equal proportion with chitosan for cutaneous application. The droplet size, zeta potential, FTIR spectra, and antifungal activity of the drug free microemulsion and drug loaded microemulsions with/without chitosan were characterized. The ex vivo drug permeation of drug loaded microemulsions with/without chitosan was compared with that of the bulk drug, using the Franz diffusion apparatus with the excised skin from Wistar rats. The droplet size of the drug free microemulsion and drug loaded microemulsions with/without chitosan were 25.53 ± 3.84 nm, 168.6 ± 13.33 nm, and 35.13 ± 0.41 nm respectively, with a polydispersity index between 0.436 and 0.658. The FTIR spectra demonstrated no changes in the structure of the drug in the drug loaded microemulsions with/without chitosan. The in vitro antifungal studies against Candida albicans exhibited similar zones of inhibition between bulk drug and drug loaded microemulsion, while the minimum inhibitory concentration showed a 2-fold decrease with drug loaded microemulsions with/without chitosan compared with the bulk drug. SEM confirmed substantial morphological changes in C. albicans cell membrane. The drug loaded microemulsion with chitosan revealed a slow and sustained release of itraconazole in phosphate buffered saline (pH 7.4) proving it to be an efficient, stable, and sustained topical delivery vehicle.

The Optimization of Collimator Material and In Vivo Testing Dosimetry of Boron Neutron Capture Therapy (BNCT) on Radial Piercing Beam Port Kartini Nuclear Reactor by Monte Carlo N-Particle Extended (MCNPX) Simulation Method

Boron Neutron Capture Therapy (BNCT) on radial piercing beam port Kartini nuclear reactor by MCNPX simulation method has been done in the National Nuclear Energy Agency Yogyakarta. BNCT is a type of therapy alternative that uses nuclear reaction 10B (n, α) 7Li to produce 2.79 MeV total kinetic energy. To be eligible IAEA conducted a study of design improvements and variations on some parameters to optimum condition which are Ni-nat thickness of 1.75 cm as collimator wall, Al2S3 as thick as 29 cm as moderator, Al2O3 0.5 cm thick as filter, Pb and Bi thickness of 4 cm as the end of the gamma shield collimators and Bi thickness of 1.5 cm as the base gamma shield collimators. The total dose was accepted in the tumor tissue 900 × 10-4 Gy/s. Radiation dose on the tumor tissue is 50±3 Gy with time irradiation of 9 minutes and 10 seconds. That dose was given into skin tissue and healthy liver tissue consecutively (6.00±0.05) × 10-2 Gy and (10.00±0.05) × 10-2 Gy. It shows the dose received by healthy tissue is still within safe limits.

Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung.

The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.

Construction and In Vivo Testing of Prokaryotic Riboregulators.

RNAs that are transcribed and self-assemble within living cells are valuable tools for regulating and organizing cellular activities. Riboregulators, in particular, have been widely used for modulating translation and transcription in response to cognate transactivating or trigger RNAs, enabling cells to evaluate logic operations and to respond to environmental cues. Herein we detail a set of methods for the rapid construction and testing of prokaryotic riboregulators in Escherichia coli. These methods enable construction of dozens of riboregulator plasmids at the same time without the use of restriction enzymes. Furthermore, they facilitate rapid screening of devices and can be applied to a variety of other self-assembling in vivo RNA systems.