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Full-Text Articles in Engineering
Nanoemulsions Within Liposomes For Cytosolic Drug Delivery To Multidrug-Resistant Cancer Cells, Jacob Brian Williams
Nanoemulsions Within Liposomes For Cytosolic Drug Delivery To Multidrug-Resistant Cancer Cells, Jacob Brian Williams
Theses and Dissertations
Cancer cells that survive chemotherapy treatment often develop resistance to the administered chemotherapeutics, as well as to many other types of drugs, because the cancer cells increase their production of efflux pumps in the cell. This undesired phenomenon of resistance to cancer drugs is known as multidrug resistance. This work uses a novel drug carrier, called an eLiposome, to achieve cytosolic drug delivery to kill multidrug-resistant cancer cells. An eLiposome consists of a perfluoropentane (PFC5) emulsion droplet inside of a liposome. Folate attached to the eLiposome facilitates uptake into the cell. The PFC5 droplet is metastable at body temperature, but …
Thermal And Convective Loading Methods For Releasing Hydrophobic Therapeutics From Contact Lenses, Ryan Ruben Horne
Thermal And Convective Loading Methods For Releasing Hydrophobic Therapeutics From Contact Lenses, Ryan Ruben Horne
Theses and Dissertations
This thesis investigates the feasibility of loading silicone hydrogel (SiHy) contact lenses with two different hydrophobic therapeutics, latanoprost and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), for treatment of glaucoma and hyperemia respectively. The two methods of loading were 1) thermal loading in an aqueous medium and 2) convective loading in a solution of n-propanol. Dailies Total1® lenses prepared in this manner were tested for their loading and their release into artificial tears. Continuous release over 1-4 days at therapeutic levels is achievable from thermal loading of DMPC, convective loading of DMPC, and convective loading of latanoprost. The DMPC loading processes can be naturally integrated …
Novel Liposomes For Targeted Delivery Of Drugs And Plasmids, Marjan Javadi
Novel Liposomes For Targeted Delivery Of Drugs And Plasmids, Marjan Javadi
Theses and Dissertations
People receiving chemotherapy not only suffer from side effects of therapeutics but also must buy expensive drugs. Targeted drug and gene delivery directed to specific tumor-cells is one way to reduce the side effect of drugs and use less amount of therapeutics. In this research, two novel liposomal nanocarriers were developed. This nanocarrier, called an eLiposome, is basically one or more emulsion droplets inside a liposome. Emulsion droplets are made of perfluorocarbons which usually have a high vapor pressure. Calcein (as a model drug) and Paclitaxel were used to demonstrate drug delivery, and plasmids and siRNA were used to exemplify …
Ultrasound-Induced Phase Change Of Emulsion Droplets For Targeted Gene And Drug Delivery, James R. Lattin
Ultrasound-Induced Phase Change Of Emulsion Droplets For Targeted Gene And Drug Delivery, James R. Lattin
Theses and Dissertations
This dissertation explores the potential of using perfluorocarbon emulsion droplets to add an ultrasound-sensitive element to drug delivery systems. These emulsion droplets may be induced to vaporize with ultrasound; during the rarefactional phase of an ultrasound wave, the pressure around the droplets may fall below the vapor pressure of the liquid forming the emulsion, providing a thermodynamic potential for vaporization. This ultrasound-induced phase change of the emulsion droplet could release therapeutics attached to the droplet surface or aid in drug delivery due to mechanical effects associated with vaporization and expansion, similar to the ability of cavitating bubbles to aid in …
Surface Modification Of Liposomes Containing Nanoemulsions, Jonathan Michael Hartley
Surface Modification Of Liposomes Containing Nanoemulsions, Jonathan Michael Hartley
Theses and Dissertations
Many attempts have been made to make cancer therapy more selective and less detrimental to the health of the patients. Nanoparticles have emerged as a way to solve some of the problems of traditional chemotherapy. Nanoparticles can provide protection for the therapeutic from degradation or clearance, as well as protection to healthy tissue from the damaging effects of chemotherapy drugs. Researchers are pursuing different strategies but all have the same goals of improving the outcomes of cancer patients. The field of controlled release of drugs has increased significantly in hopes of better treating diseases like cancer. Improved control of drug …
Ultrasonic Drug Delivery To Tumors Via Stealth Liposomes, Peter Jones, Ghaleb A. Husseini, William G. Pitt, Beverly L. Roeder
Ultrasonic Drug Delivery To Tumors Via Stealth Liposomes, Peter Jones, Ghaleb A. Husseini, William G. Pitt, Beverly L. Roeder
Faculty Publications
Our research develops ultrasonically-controlled drug delivery systems. Previous micellar drug carriers released the drug upon ultrasonication. We have developed a liposomal drug carrier that is even more effective upon insonation in reducing tumors.
Nano-Polymeric Carrier Influences Ultrasonic Drug Delivery To Tumors, Odgerel Badamjav, Ghaleb A. Husseini, Peter Jones, William G. Pitt, Beverly L. Roeder
Nano-Polymeric Carrier Influences Ultrasonic Drug Delivery To Tumors, Odgerel Badamjav, Ghaleb A. Husseini, Peter Jones, William G. Pitt, Beverly L. Roeder
Faculty Publications
Our overall research goal is to alleviate the severe side effects of chemotherapy while enhancing the effectiveness of the treatment by localizing the delivery of anti-cancer drugs to the cancer tissue only. To this end we are synthesizing ultrasonically-activated delivery systems that can control drug delivery in space and time. Ultrasound (US) is non-invasive (no surgery required) and can be focused on the specific tissue to be treated. Our past research has developed a nano-sized polymeric drug carrier that sequesters the therapeutic drug, such as Doxorubicin (Dox), within the carrier and releases the drug upon insonation by ultrasound. This drug-containing …
Ultrasonically-Assisted Drug Delivery In Rats Reduces Tumor Growth, William G. Pitt, Beverly L. Roeder, G. Bruce Schaalje, Bryant J. Staples
Ultrasonically-Assisted Drug Delivery In Rats Reduces Tumor Growth, William G. Pitt, Beverly L. Roeder, G. Bruce Schaalje, Bryant J. Staples
Faculty Publications
Previously we have shown that nanosized drug carriers called Plurogels™ sequestered Doxorubicin (Dox) and partially released this drug with application of ultrasound (US) (Fig. 1)1. The application to chemotherapy was successfully demonstrated in a rat tumor model2. However previous studies did not examine the distribution of Dox in the insonated and control tissue. This recent work investigated the effect of two US frequencies and examined the Dox distribution in the insonated and control tumors to determine if US was depositing more Dox at the insonated site.
Pharmacokinetics Of Ultrasonically-Released, Micelle-Encapsulated Doxorubicin In The Rat Model And Its Effect On Tumor Growth, Bryant J. Staples
Pharmacokinetics Of Ultrasonically-Released, Micelle-Encapsulated Doxorubicin In The Rat Model And Its Effect On Tumor Growth, Bryant J. Staples
Theses and Dissertations
Chemotherapy is one of the most successful cancer treatments used today. Unfortunately, the amount of chemotherapy a patient can receive is limited by the associated negative side effects, such as cardiotoxicity, immune system suppression, and nephrotoxicity. Encapsulation of these drugs, Doxorubicin (DOX) in particular, in stabilized Pluronic micelles (Plurogel TM) shows success in limiting these harmful side effects. In previous studies, low-frequency ultrasound (US) has been shown, in vitro, to locally release DOX from these micelles. In this study, a novel drug delivery system involving the encapsulation of DOX in Plurogel and the release of the drug at the tumor …
High-Frequency Ultrasound Drug Delivery And Cavitation, Mario Alfonso Diaz
High-Frequency Ultrasound Drug Delivery And Cavitation, Mario Alfonso Diaz
Theses and Dissertations
The viability of a drug delivery system which encapsulates chemotherapeutic drugs (Doxorubicin) in the hydrophobic core of polymeric micelles and triggers release by ultrasound application was investigated at an applied frequency of 500 kHz. The investigation also included elucidating the mechanism of drug release at 70 kHz, a frequency which had previously been shown to induce drug release. A fluorescence detection chamber was used to measure in vitro drug release from both Pluronic and stabilized micelles and a hydrophone was used to monitor bubble activity during the experiments. A threshold for release between 0.35 and 0.40 in mechanical index was …
The Role Of Cavitation In Acoustically Activated Drug Delivery, Mario A. Diaz, Ghaleb A. Husseini, William G. Pitt, Eric S. Richardson, Douglas A. Christensen
The Role Of Cavitation In Acoustically Activated Drug Delivery, Mario A. Diaz, Ghaleb A. Husseini, William G. Pitt, Eric S. Richardson, Douglas A. Christensen
Faculty Publications
The triblock copolymer, Pluronic P105, has been found to be an ideal ultrasonically activated drug delivery vehicle because it forms micelles with hydrophobic polypropylene oxide cores that sequester hydrophobic drugs (Fig. 1). These micelles release their contents upon the application of low frequency ultrasound [1]such that drugs can be released specifically at the ultrasonicated region (Fig. 2). Such ultrasonically controlled release has been effective against cancer cells in vitro [2] and in vivo [3]. This poster presents our results showing that collapse cavitation is associated with drug release. Cavitation is generally divided into two types of behavior. Stable cavitation is …
Stable Polymer Micelle Systems As Anti-Cancer Drug Delivery Carriers, Yi Zeng
Stable Polymer Micelle Systems As Anti-Cancer Drug Delivery Carriers, Yi Zeng
Theses and Dissertations
Several temporarily stable polymer micelle systems that might be used as ultrasonic-activated drug delivery carriers were synthesized and investigated. These polymeric micelle systems were Plurogel®, Tetronic®, poly(ethylene oxide)-b-poly(N-isopropylacrylamide) and poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactaten). In previous work in our lab, Pruitt et al. developed a stabilized drug carrier named Plurogel® [5, 6]. Unfortunately, the rate of the successful Plurogel® synthesis was only about 30% by simply following Pruitt's process. In this work, this rate was improved to 60% by combining the process of adding 0.15 M NaCl and/or 10 µl/ml n-butanol and by preheating the solution before polymerization. Tetronics® were proved not …
Mechanism Of Targeted Chemotherapeutic Delivery Using Ultrasound, Thaidra A. Gaufin, Byron K. Murray, Seiga Ohmine, Kim L. O'Neill, William G. Pitt, Briant S. Stringham
Mechanism Of Targeted Chemotherapeutic Delivery Using Ultrasound, Thaidra A. Gaufin, Byron K. Murray, Seiga Ohmine, Kim L. O'Neill, William G. Pitt, Briant S. Stringham
Faculty Publications
Ultrasound (US) is used to enhance and target delivery of drugs and genes to cancer tissues. The advantages of focused delivery to select tissues are manifold, but the exact mechanisms are largely unknown and need clarification to optimize delivery. The present study further defined the role of collapse cavitation in US-induced permeabilization of cell membranes and subsequent drug or gene uptake by the cell. Cavitation, defined as the collapse of micro-bubbles, produces high shear stresses and shock waves that may transiently puncture cell membranes and has been suggested as the cause of increased permeability. The hypothesis that collapsing bubbles permeabilize …