Thermoablation of Malignant Kidney Tumors Using Magnetic Nanoparticles: An In Vivo Feasibility Study in a Rabbit Model

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.

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Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180313154724 ◽

2018 ◽

Vol 18 (8) ◽

pp. 1138-1147 ◽

Cited By ~ 1

Author(s):

Esra Metin ◽

Pelin Mutlu ◽

Ufuk Gündüz

Keyword(s):

Breast Cancer ◽

Polyethylene Glycol ◽

Magnetic Nanoparticles ◽

Cancer Treatment ◽

Cancer Cells ◽

Drug Loading ◽

Gravimetric Analysis ◽

Polyethylene Glycol 1000 ◽

Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

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Unraveling the molecular pathobiology of vocal fold systemic dehydration using an in vivo rabbit model

PLoS ONE ◽

10.1371/journal.pone.0236348 ◽

2020 ◽

Vol 15 (7) ◽

pp. e0236348

Author(s):

Naila Cannes do Nascimento ◽

Andrea P. dos Santos ◽

M. Preeti Sivasankar ◽

Abigail Cox

Keyword(s):

Vocal Fold ◽

Rabbit Model

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Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

Scientific Reports ◽

10.1038/s41598-021-89830-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karen E. Beenken ◽

Mara J. Campbell ◽

Aura M. Ramirez ◽

Karrar Alghazali ◽

Christopher M. Walker ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bone Defect ◽

Rabbit Model ◽

In Vivo Studies ◽

Bovine Bone ◽

Bone Filler ◽

Antibiotic Release ◽

Local Antibiotic ◽

Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

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Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

Microcirculation ◽

10.1111/micc.12678 ◽

2021 ◽

Author(s):

Evgenii Belykh ◽

Xiaochun Zhao ◽

Brandon Ngo ◽

Dara S. Farhadi ◽

Adam Kindelin ◽

...

Keyword(s):

Blood Flow ◽

Feasibility Study ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Brain Microvasculature

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β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00261-0 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Guoying Zhang ◽

Cheng Xue ◽

Yiming Zeng

Keyword(s):

Cell Cycle ◽

Cell Viability ◽

Cell Model ◽

Protective Efficacy ◽

Rabbit Model ◽

Akt Pathway ◽

Loss Of Function ◽

Airway Stenosis

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

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Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

Scientific Reports ◽

10.1038/s41598-021-85348-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoonhee Kim ◽

Yoon Bum Lee ◽

Seung Kuk Bae ◽

Sung Suk Oh ◽

Jong-ryul Choi

Keyword(s):

Ischemic Stroke ◽

Brain Damage ◽

Rabbit Model ◽

Specific Area ◽

Brain Atlas ◽

Rabbit Brain ◽

Stroke Model ◽

Triphenyltetrazolium Chloride ◽

Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

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Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics13040444 ◽

2021 ◽

Vol 13 (4) ◽

pp. 444

Author(s):

Alaa Mahran ◽

Sayed Ismail ◽

Ayat A. Allam

Keyword(s):

Triamcinolone Acetonide ◽

Delivery System ◽

Histopathological Examination ◽

Rabbit Model ◽

Subconjunctival Injection ◽

In Vivo Evaluation ◽

Ternary Phase Diagrams ◽

Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

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Silane-Coating Strategy for Titanium Functionalization Does Not Impair Osteogenesis In Vivo

Materials ◽

10.3390/ma14071814 ◽

2021 ◽

Vol 14 (7) ◽

pp. 1814

Author(s):

Plinio Mendes Senna ◽

Carlos Fernando de Almeida Barros Mourão ◽

Rafael Coutinho Mello-Machado ◽

Kayvon Javid ◽

Pietro Montemezzi ◽

...

Keyword(s):

Bone Formation ◽

Photoelectron Spectroscopy ◽

Titanium Surface ◽

Rabbit Model ◽

Biologically Active ◽

Force Microscopy ◽

Atomic Force ◽

Silane Coating ◽

Titanium Screws

Silane-coating strategy has been used to bind biological compounds to the titanium surface, thereby making implant devices biologically active. However, it has not been determined if the presence of the silane coating itself is biocompatible to osseointegration. The aim of the present study was to evaluate if silane-coating affects bone formation on titanium using a rabbit model. For this, titanium screw implants (3.75 by 6 mm) were hydroxylated in a solution of H2SO4/30% H2O2 for 4 h before silane-coating with 3-aminopropyltriethoxysilane (APTES). A parallel set of titanium screws underwent only the hydroxylation process to present similar acid-etched topography as a control. The presence of the silane on the surface was checked by x-ray photoelectron spectroscopy (XPS), with scanning electron microscopy (SEM) and atomic force microscopy (AFM). A total of 40 titanium screws were implanted in the tibia of ten New Zealand rabbits in order to evaluate bone-to-implant contact (BIC) after 3 weeks and 6 weeks of healing. Silane-coated surface presented higher nitrogen content in the XPS analysis, while micro- and nano-topography of the surface remained unaffected. No difference between the groups was observed after 3 and 6 weeks of healing (p > 0.05, independent t-test), although an increase in BIC occurred over time. These results indicate that silanization of a titanium surface with APTES did not impair the bone formation, indicating that this can be a reliable tool to anchor osteogenic molecules on the surface of implant devices.

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Effect of valproic acid on functional bleb morphology in a rabbit model of minimally invasive surgery

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-318691 ◽

2021 ◽

pp. bjophthalmol-2020-318691

Author(s):

Zhu Li Yap ◽

Li-Fong Seet ◽

Stephanie WL Chu ◽

Li Zhen Toh ◽

Farah Ilyana Ibrahim ◽

...

Keyword(s):

Valproic Acid ◽

Cell Growth ◽

Minimally Invasive ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Rabbit Model ◽

Terminal Deoxynucleotidyl Transferase ◽

Label Free ◽

Collagen Fibres

AbstractPurposeTo determine the effect of valproic acid (VPA) on bleb morphology and scar characteristics in a rabbit model of minimally invasive glaucoma surgery (MIGS).MethodsNine New Zealand white rabbits were subjected to MIGS with intraoperative implantation of the PreserFlo MicroShunt. Rabbits were then administered with subconjunctival injections of phosphate buffered saline (PBS) (n=4) or with VPA (n=5). Bleb morphology was examined by slit-lamp biomicroscopy and in vivo confocal microscopy. Postoperative day 28 tissues were examined by immunohistochemical evaluation and label-free multiphoton microscopy to visualise the collagen matrix, by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay and immunofluorescent labelling for Ki67 expression to detect apoptosis and cell growth, and by real-time quantitative PCR to measure Col1a1, Fn, and Smad6 transcript expression.ResultsVPA-treated blebs were detectable on day 28, while the PBS-treated blebs were not detectable by day 14. VPA-treated blebs were diffuse, extended posteriorly with near normal conjunctival vascularity and featured a combination of reticular/blurred stromal pattern with evidence of relatively large stromal cysts. Instead of the deposition of thick, disorganised collagen fibres characteristic of the PBS bleb, the VPA bleb contained conspicuously thinner collagen fibres which were associated with similarly thinner fibronectin fibres. In corroboration, Col1a1 and Fn mRNA expression was reduced in the VPA blebs, while increased Smad6 expression implicated the disruption of the transforming growth factor beta pathway. Apoptosis and cell growth profiles appeared similar with both treatments.ConclusionsThe results support the application of VPA to enhance bleb morphology associated with good bleb function in MIGS with no apparent cytotoxicity.

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