Chemical Engineering Commons^™

Removal Of Retained Electrospinning Solvent Prolongs Drug Release From Electrospun Plla Fibers, Anthony R. D'Amato, Nicholas J. Schaub, Jesus M. Cardenas, Andrew S. Fiumara, Paul M. Troiano, Andrea Fischetti, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

A major challenge in developing drug-releasing electro spun nanofibers is obtaining long-term drug release over many weeks with no burst release of drug. Here, we present new methods capable of prolonging the diffusive release of small molecule drugs from electro spun poly-L-lactic acid (PLLA) nanofibers. The methods focus on removal of retained electrospinning solvent through fiber heating, maintaining fibers in a laboratory setting, or a combination of these methods. These post-fabrication methods altered the release characteristics of a model small molecule drug, 6-aminonicotinamide (6AN), from PLLA fibers. Specifically, untreated fibers released 6AN over 9 days, and fibers that underwent a …

Biomaterials For Local, Controlled Drug Delivery To The Injured Spinal Cord, Alexis M. Ziemba, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present …

Synthesis And Characterization Of Poly(Simvastatin) - Incorporated Copolymers And Blends For Bone Regeneration, Theodora Asafo-Adjei

Theses and Dissertations--Biomedical Engineering

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release.

Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) …

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

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 …

Ionic Driven Embedment Of Hyaluronic Acid Coated Liposomes In Polyelectrolyte Multilayer Films For Local Therapeutic Delivery, Stephen Lawrence Hayward, David Francis, Matthew J. Sis, Srivatsan Kidambi

UCARE: Research Products

The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-LLysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited …

Biopolymeric Mucin And Synthetic Polymer Analogs: Their Structure, Function And Role In Biomedical Applications, Sundar Prasanth Authimoolam, Thomas D. Dziubla

Chemical and Materials Engineering Faculty Publications

Mucin networks are viscoelastic fibrillar aggregates formed through the complex self-association of biopolymeric glycoprotein chains. The networks form a lubricious, hydrated protective shield along epithelial regions within the human body. The critical role played by mucin networks in impacting the transport properties of biofunctional molecules (e.g., biogenic molecules, probes, nanoparticles), and its effect on bioavailability are well described in the literature. An alternate perspective is provided in this paper, presenting mucin’s complex network structure, and its interdependent functional characteristics in human physiology. We highlight the recent advances that were achieved through the use of mucin in diverse areas of bioengineering …

Engineering Of Lipid Nanoparticles For Advanced Drug Deilvery Applications, Stephen L. Hayward

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

‘Nanomedicine’, the application of nanotechnology principles to the field of medicine, has stimulated the development of nano-platforms for next generation drug delivery. By exploiting nanoscale properties of materials to selectively alter intrinsic characteristics of therapeutics, researchers have improved the efficacy and pharmacokinetic profiles for a variety of drug types. Despite preliminary commercial and clinical success, there still remains a need to develop an improved delivery platform that can provide high cargo entrapment, efficient intracellular delivery, evasion of intracellular degradation pathways, and provide cell population specific targeting.

In this study we engineered a nanocarrier system composed of a core bilayer structure …

Insights Into Ultrasonic Release From Eliposomes, Marjan Javadi, William G. Pitt

Faculty Publications

A novel nanosized liposomal carrier was prepared consisting of perfluorocarbon emulsion droplet(s) encapsulated inside a liposome, which is called an eLiposome. This 200-nm construct is useful for acoustically activated drug delivery because ultrasound causes the emulsion droplet to expand from liquid to gas, which expansion ruptures the eLiposome bilayer and releases the internal contents. This study focuses on the parameters that influence control of the release of calcein (a model drug), including ultrasound amplitude, insonation time, and perfluorocarbon vapor pressure as a function of temperature and composition. The results show that calcein release increases as the ultrasound amplitude or insonation …

Biomimetic Oral Mucin From Polymer Micelle Networks, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated …

Synthetic Materials With Redox-Triggers For Imaging And Drug Delivery, Jungeun Bae

Electronic Theses and Dissertations

Synthetic materials embedded with stimuli-responsive cleavable bonds have been extensively utilized for the development of site-targeted drug delivery system and selective imaging reporters. We developed stimuli-sensitive materials with two different redox switches including trimethyl-locked quinone propionic acid and nitrobenzyl moieties. Novel redox-sensitive polymeric nanoparticles and micelles were prepared from a synthesized monomer containing trimethyl-locked quinone propionic acid as a redox trigger. A hydrophobic cancer drug, Paclitaxel, was incorporated into the redox-responsive polymeric nanoparticles and micelles prepared from the synthesize polymers. The effect of redox stress on the nanoparticles and micelles was evaluated with a chemical reductant, sodium dithionite demonstrating that …

Determining The Critical Micelle Concentration Of Polymer Matrix For Drug Delivery Purposes, Katie Emmert

Williams Honors College, Honors Research Projects

Targeted oral release systems have been a large topic within drug delivery systems. There are several benefits to an oral delivery including patient convenience and lower chance of infection. The colon specifically has been researched as the release media. The colon is an ideal location for a release because the pH is stable with high levels of microorganisms. Like any type of drug delivery research, there are several hurdles to overcome. In order for a drug to be released in the colon, the drug must survive the stomach and be biocompatible. This biocompatibility and pH sensitivity was created using a …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

Encapsulating Liposomes For Stabilized Drug Delivery, Corbin Jacobs, Dr. William Pitt

Journal of Undergraduate Research

Liposomes are tiny vesicles composed of materials similar to a cell membrane’s bilayer and “are useful for delivering anticancer agents to tumors and reducing the severe side effects of the agents.”1 Following synthesis, liposomes containing drug are administered intravenously. Fortunately, tumors have hyperpermeable vasculature which facilitates liposomal accumulation by their leaking out of the capillaries surrounding the tumor.2 Once near the tumor, individual cells will endocytose or engulf the vesicles as long as they are between 10 nm and 1000 nm.3

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 …

Computer Modeling And Mapping Of Ultrasound Intensity In Human Tissues For Gene And Drug Delivery, Spencer Smith, Dr. William Pitt

Journal of Undergraduate Research

Over the past years ultrasound has been used extensively in medical treatments. It is now being developed and tested in localized drug and gene delivery. One of the main applications for drug delivery is treating cancer.

Particle Shape Enhances Specificity Of Antibody-Displaying Nanoparticles, Sutapa Barua, Jin-Wook Yoo, Poornima Kolhar, Aditya Wakankar, Yatin R. Gokarn, Samir Mitragotri

Chemical and Biochemical Engineering Faculty Research & Creative Works

Monoclonal antibodies are used in numerous therapeutic and diagnostic applications; however, their efficacy is contingent on specificity and avidity. Here, we show that presentation of antibodies on the surface of nonspherical particles enhances antibody specificity as well as avidity toward their targets. Using spherical, rod-, and disk-shaped polystyrene nano- and microparticles and trastuzumab as the targeting antibody, we studied specific and nonspecific uptake in three breast cancer cell lines: BT-474, SK-BR-3, and MDA-MB-231. Rods exhibited higher specific uptake and lower nonspecific uptake in all cells compared with spheres. This surprising interplay between particle shape and antibodies originates from the unique …

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

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 …

Theoretical Prediction Of Drug Release In Gi Tract From Spherical Matrix Systems, Naga Lakshmi Ramana Susarla

Dissertations

The significance of controlled release drug delivery systems (CRDDS) lies in their ability to deliver the drug at a steady rate thus reducing the dosage interval and providing a prolonged pharmacodynamic effect. But despite the steadily increasing practical importance of these devices, little is known regarding their underlying drug release mechanisms. Mathematical modeling of these drug delivery systems could help us understand the underlying mass transport mechanisms involved in the control of drug release. Mathematical modeling also plays an important role in providing us with valuable information such as the amount of drug released during a certain period of time …

Study Of Controlled Release Of Active Pharmaceutical Ingredients From Functionalized Nanoclays And Polymer Matrices, Jin Uk Ha

Dissertations

This dissertation contains the results of three related novel investigations in the field of structure-property-processing relationships of pharmaceutical polymer-based products. They are: a) modification of a pharmaceutical anionic nanoclay with two different Active Pharmaceutical Ingredients (APIs) to produce nanohybrid API carriers intended to be used alone or in acrylic polymer matrices, b) comparison of binary systems containing the above APIs in the selected acrylic polymers in terms of their miscibilities with the polymer, but in the absence of nanoclay, and c) comparison of the polymer/API binary systems with ternary polymer/API/Clay systems.

For the first study, the calcination method which can …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Sneha Reddy Kuthuru

All Capstone Projects

Recent clinical studies have shown the importance of folate receptor in drug delivery system as they increase the potency and reduce toxicity of many cancer therapies. The folate receptor alpha ( FR-a) binds with high affinity for folic acid and serves for receptor mediated transport of folate into cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased requirement for folic acid. It is known that FR-a levels are elevated in specific malignant diseases (solid tumors, leukemia) and thus the FR receptor serves as useful targeting moiety for the diagnosis …

Design Of Drug Delivery Strategies Based On Well-Stirred Experiments, Kumud Kanneganti

Theses

Drugs are generally administered to the human body via injections (IV) or through other paths such as the buccal, nasal routes. The main consideration when designing a medication schedule is to maintain a therapeutic level of the drug in the body during the course of treatment. To achieve this goal, when IV drug therapy is selected, particular importance has to given to the dose to be injected and how to maintain the concentration of the pharmaceutical active ingredient (API) in the body between a Minimum Toxic Concentration (MTC) and a Minimum Effective Concentration (MEC). This therapeutic range varies with the …

Surface Engineering Of Macrophages With Nanoparticles To Generate A Cell-Nanoparticle Hybrid Vehicle For Hypoxia-Targeted Drug Delivery, Christopher A. Holden, Quan Yuan, W. Andrew Yeudall, Deborah A. Lebman, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug …

Remote Controlled Hydrogel Nanocomposites: Synthesis, Characterization, And Applications, Nitin S. Satarkar

University of Kentucky Doctoral Dissertations

There is significant interest in the development of hydrogels and hydrogel nanocomposites for a variety of biomedical applications including drug delivery, sensors and actuators, and hyperthermia cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled (RC) actuation. In this dissertation, the development of hydrogel nanocomposites containing magnetic nanoparticles/carbon nanotubes, actuation with remote stimulus, and some of their applications are highlighted.

The primary hydrogel nanocomposite systems were synthesized by incorporation of magnetic nanoparticles into temperature responsive N-isopropylacrylamide (NIPAAm) matrices. Various nanocomposite properties …

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.

Encapsulation And Extended Release Of Anti-Cancer Anastrozole By Stealth Nanoparticles, Kumkum Sarkar, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

To improve delivery efficiency of anastrozole, we applied dendrimer-based stealth nanoparticles to encapsulate anastrozole to formulate stealth anastrozole nanoparticles. This work demonstrated that stealth nanoparticles composed of a PAMAM dendrimers core and a PEG layer could encapsulate anastrozole, hence causing improved water solubility of anastrozole. Anastrozole encapsulation depended on concentration of stealth nanoparticles and generation of dendrimer. The extended release of anastrozole was achieved. We envisioned that this highly structurally adaptable stealth nanoparticle could be further biofunctionalized to construct a targeted therapeutic delivery system for breast cancer treatment.

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

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

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 …