Matching Items (43)

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Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic effect

Description

With the advancement of a growing number of oncolytic viruses (OVs) to clinical development, drug delivery is becoming an important barrier to overcome for optimal therapeutic benefits. Host immunity, tumor

With the advancement of a growing number of oncolytic viruses (OVs) to clinical development, drug delivery is becoming an important barrier to overcome for optimal therapeutic benefits. Host immunity, tumor microenvironment and abnormal vascularity contribute to inefficient vector delivery. A number of novel approaches for enhanced OV delivery are under evaluation, including use of nanoparticles, immunomodulatory agents and complex viral–particle ligands along with manipulations of the tumor microenvironment. This field of OV delivery has quickly evolved to bioengineering of complex nanoparticles that could be deposited within the tumor using minimal invasive image-guided delivery. Some of the strategies include ultrasound (US)-mediated cavitation-enhanced extravasation, magnetic viral complexes delivery, image-guided infusions with focused US and targeting photodynamic virotherapy. In addition, strategies that modulate tumor microenvironment to decrease extracellular matrix deposition and increase viral propagation are being used to improve tumor penetration by OVs. Some involve modification of the viral genome to enhance their tumoral penetration potential. Here, we highlight the barriers to oncolytic viral delivery, and discuss the challenges to improving it and the perspectives of establishing new modes of active delivery to achieve enhanced oncolytic effects.

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  • 2017-11-08

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Structure-function study of N-isopropylacrylamide copolymers with enzyme degradable GAPGLF and GAPGLL side chains

Description

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.

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Date Created
  • 2018-05

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Taste Through Travel

Description

This thesis creative project shares a food and travel blog through a published website that follows my friends and I while we travel through North America reviewing foods that are

This thesis creative project shares a food and travel blog through a published website that follows my friends and I while we travel through North America reviewing foods that are found in certain areas. This internet blog outlines local cuisines and what makes them unique to certain locations.
Through my personal travels and peer interviews, I have found that this project gave me the opportunity to expand my knowledge on different cultures and regions of the North America and explore how local foods contribute to the cultures in that setting. Additionally, this thesis helped me self-teach myself how to develop a fully published website and practice my web design skills.

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Date Created
  • 2020-05

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Ultrasound Sensitive Injectable Materials

Description

In an embolization therapy, a material is injected into a vessel to block blood flow. While this therapy is useful in starving cancerous cells it can be dangerous, with some

In an embolization therapy, a material is injected into a vessel to block blood flow. While this therapy is useful in starving cancerous cells it can be dangerous, with some blockades in the brain dislodging and causing strokes or blindness. Currently, embolic materials on the market such as metal coils, balloons, and liquid embolic agents do not have a quick removal procedure. An ultrasound cleavable material could be removed in an emergency situation without invasive surgery. The primary goal of this research is to design and synthesize a polymer that can be broken down by high intensity focused ultrasound (HIFU). Initially, we have tested the ultrasound sensitive qualities on PPODA-QT hydrogel, a common embolic agent, but the gel showed no physical change after HIFU exposure. It is theorized that PNIPAAm combined with HIFU sensitive monomers can develop a temperature and ultrasound sensitive embolic agent. In our studies, poly(NIPAAm-co-tBa) had a slight lower critical solution temperature (LCST) change of about 2˚C from before to after HIFU while the study with poly(NIPAAm-co-ACL-BME) and PPODA-QT showed no change in LCST.

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Date Created
  • 2020-05

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NIPAAm co-DEAEMA Hydrogels Prolong Ketorolac Release

Description

NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved

NIPAAm co-DEAEMA hydrogels are a potential solution for sustained, local delivery of ketorolac tromethamine. Current methods of postoperative pain management, such as local anesthetics, NSAIDs, and opioids, can be improved by minimizing side effects while still effectively treating severe and extreme pain. Though high doses of ketorolac can be toxic, sustained, local delivery via hydrogels offers a promising solution. Four ketorolac release studies were conducted using PNDJ hydrogels formulated by Sonoran Biosciences. The first two studies tested a range of JAAm concentration between 1.4 and 2.2 mole percent. Both had high initial release rates lasting less than 7 days and appeared to be unaffected by JAAm content. Tobramycin slowed down the release of ketorolac but was unable to sustain release for more than 6 days. Incorporating DEAEMA prolonged the release of ketorolac for up to 14 days with significant reductions in initial burst release rate. Low LCST of NIPAAM co-DEAEMA polymer is problematic for even drug distribution and future in vivo applications.

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Date Created
  • 2020-05

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Thermo-Responsive poly(N-isopropylacrylamide)-Based Polymers for Endovascular Brain Aneurysm Repair

Description

There is an increasing interest in developing thermo-responsive polymers for treating aneurysms. In this thesis project, the potential for poly(NIPAAm-co-JAAm-co-HEMA-Acrylate) (PNJHAc) as a treatment method for brain aneurysms was investigated.

There is an increasing interest in developing thermo-responsive polymers for treating aneurysms. In this thesis project, the potential for poly(NIPAAm-co-JAAm-co-HEMA-Acrylate) (PNJHAc) as a treatment method for brain aneurysms was investigated. Five different batches of polymer were synthesized, purified, lyophilized, and characterized using nuclear magnetic resonance and cloud point techniques over the course of several months. Two were tested in aneurysm models. Of these five batches, there were two that showed promise as liquid embolic agents for endovascular embolization.

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Date Created
  • 2020-05

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The Effects of Material and Surface Properties on the Antimicrobial Susceptibility of Staphylococcal Biofilms

Description

Biofilm derived orthopedic infections are increasingly common after contamination of an open bone fracture or the surgical site pre- and post-orthopedic prosthetic insertion or removal. These infections are usually difficult

Biofilm derived orthopedic infections are increasingly common after contamination of an open bone fracture or the surgical site pre- and post-orthopedic prosthetic insertion or removal. These infections are usually difficult to eradicate due to the resistant nature of biofilms to antimicrobial therapy. Difficulty of treatment of biofilm derived infections is also partly due to the presence of persister cells in the biofilm matrix. Persister cells are tolerant to antimicrobial therapy delivered via the systemic route. It is thus possible for these cells to repopulate their environment once systemic antimicrobial delivery is discontinued. The antimicrobial concentration required to eradicate bacterial biofilms, minimum biofilm eradication concentration (MBEC), can be determined in vitro by exposing biofilms to different regimens of antimicrobial solutions. Previous studies have demonstrated that values of the MBEC vary depending on the material and surface the biofilm grows on. This study investigated the relationship between antimicrobial susceptibility and antimicrobial exposure time, and the effects of surface material type on the antimicrobial susceptibility of staphylococcal biofilms. It was concluded that antimicrobial susceptibility increases with increased antimicrobial exposure time, and that the investigated surface and material properties did not have an effect on the susceptibility of staphylococcal biofilms to antimicrobial therapy. Further investigation is however necessary to confirm these results due to some inconsistent data obtained over the course of the trials.

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Date Created
  • 2016-05

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Norepinephrine and Adenosine Infused Microparticles for Brown Adipose Tissue Stimulation

Description

With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid)

With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.

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Date Created
  • 2018-12

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Investigating the Role Of VEGF in Preeclampsia

Description

Preeclampsia is a condition which arises during pregnancy and can lead to serious, even fatal, complications for the mother and baby. Annually, preeclampsia is responsible for about 50,000 total deaths

Preeclampsia is a condition which arises during pregnancy and can lead to serious, even fatal, complications for the mother and baby. Annually, preeclampsia is responsible for about 50,000 total deaths worldwide, and countless other complications for both the mother and fetus. While high blood pressure and protein in the urine are key features, symptoms vary widely, and thus understanding, diagnosing, and treating the condition is of paramount importance. Due to the correlation between preeclampsia and high blood pressure, multiple groups have studied the role of angiogenic growth factors and preeclampsia. We performed an advanced PubMed search to select studies with both preeclampsia and VEGF, a key growth factor for angiogenesis, in the title. The results of examining a total of 65 articles led to the formation of this review article to articulate the studies as a whole and state of the research on VEGF and preeclampsia to date.

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Date Created
  • 2020-05

Explaining the Prevalence of Lumbar Spine Injuries in Collegiate Football Players

Description

In terms of overall athleticism, other than the obvious extremities that take on more skillful duties in performance (arms, legs, fingers ie.), the back, specifically lower, is pivotal in athletic

In terms of overall athleticism, other than the obvious extremities that take on more skillful duties in performance (arms, legs, fingers ie.), the back, specifically lower, is pivotal in athletic movement. The main bolstering force in the lower back is the lumbar vertebrae, which on the upper end are connected to the thoracic portion of the spine, and on the lower end transform into the various processes of the sacrum. The lower back is highly involved in bending and stabilizing during athletic movement, while also being favorably responsible for not only producing but absorbing force as well. Men’s Football has the highest rate of occurrence in injuries compared to all other collegiate sports (Hassebrock 2019). This is a product of the various specificities of the game of football such as groundbreaking speed and strength, along with some psychological group-centered constructs. In survey findings, 83% healthcare professionals say that the best active treatment plan is strengthening the core muscles. While in terms of natural and technological treatments like acupuncture, contrast immersion, and electrical stimulation, there wasn’t a definitive methodology proven to be superior to the others. Allowing for the healthcare professional to be creative in their combination of treatments, as long as core strengthening is primarily targeted.

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Date Created
  • 2020-05