Biomedical Engineering and Bioengineering Commons^™

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 …

Synthesis Of Multilayered Microparticles For Targeted Drug Delivery, Elizabeth Mercer

Open Access Theses

Microparticles have been shown to be valuable in targeted drug delivery which can lead to an increased dose delivered to a targeted location, reduced patient side effects, and improved patient outcomes. The designed multilayered microparticles have the clinical application to deliver hydrophobic drugs to a targeted area. The composition of the microparticles consists of a poly-lactic acid (PLA) polymer core surrounded by a polymeric shell composed of Poly(lactic-co-glycolic acid)-Poly(ethylene glycol)-Maleimide(PLGA-PEG-Mal). The maleimide promotes conjugation of the collagen binding peptide, SILY. Targeting to type I collagen allows for this microparticle system to attach to exposed collagen in atherosclerotic vessels.

A novel …

Evaluation Of Methods To Account For Release From Nanofiber Scaffolds, Jennifer Moy

Theses

Electrospinning is a common technique utilized to form fibers from the micro- to nanometer range. Nanofibers form through electrospinning can be utilized as scaffolds since the fiber structures are similar to the structures within the extracellular matrix. Researchers use additives, such as growth factors, to help facilitate cell proliferation and function. Also, researchers are attempting to use electrospun fibers for drug delivery and as wound dressings since the electrospun fibers have high surface area to volume ratio. In both situations, the release of either the additive or the drug needs to be controlled so that the fibers would release the …

Bioactivity And Cell-Mediated Targeting Of Multistage Nanoporous Silicon Particles, Jonathan O. Martinez

Dissertations and Theses (Open Access)

Progress in drug delivery approaches have not adequately translated into clinical advances in the diagnosis or treatment of inflammatory disorders (e.g., cancer). This disconnect is rooted in the inefficient delivery of imaging and therapeutic agents to the inflamed site upon systemic delivery. A multitude of biological barriers pose insurmountable obstacles limiting the ability of the agent to effectively reach and accumulate at the target site. Nanoparticles (NP) surfaced as potential vectors to encapsulate and deliver biological agents. However, even after surface decoration, NP have failed to evade biological barriers (i.e., MPS) and to accumulate at the tumor site at therapeutic …

Synthesis And Characterization Of Clickable Dendrimer Hydrogels For Ocular Drug Delivery, Jingfei Tian

Theses and Dissertations

Topical medication is a standard treatment for glaucoma. However, frequent dosing makes the therapy inconvenient and patient unfriendly. There is a great need to develop new topical formulations that provide long lasting noninvasive drug release. In this thesis, novel clickable dendrimer hydrogels for anti-glaucoma drug delivery were synthesized and characterized. Polyamidoamine (PAMAM) dendrimers have been widely applied for drug delivery. The physical characteristics they possess include monodispersity, water solubility, encapsulation ability, and a large number of surface groups. Polycationic PAMAM dendrimer G3 was surface modified with alkyne-PEG5-acid and then reacted with polyethylene glycol bisazide (PEG-BA, 1100 gmol-1) through click chemistry …

Development And Application Of Biomimetic Electrospun Nanofibers In Total Joint Replacement, Wei Song

Wayne State University Dissertations

Failure of osseointegration (direct anchorage of an implant by bone formation at the bone-implant surface) and implant infection (such as that caused by Staphylococcus aureus, S. aureus) are the two main causes of implant failure and loosening. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. A better understanding of the key factors that influence cell fate decisions at the bone-implant interface is required. Our study is to develop a class of "bone-like" nanofibers (NFs) that promote osseointegration while preventing …

Mammalian Cells Preferentially Internalize Hydrogel Nanodiscs Over Nanorods And Use Shape-Specific Uptake Mechanisms, Rachit Agarwal, Vikramjit Singh, Patrick Jurney, Li Shi, S. Sreenivasan, Krishnendu Roy

Faculty Publications

Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. …

Semi-Interpenetrating Network Gelatin Fiber Sca Old For Oral Mucosal Delivery Of Insulin, Leyuan Xu

Theses and Dissertations

Common therapy for diabetes mellitus is subcutaneous administration of insulin that is subject to serious disadvantages, such as patient noncompliance and occasional hypoglycemia. Hence, oral administration of insulin could be more convenient and serve as a desired route. However, oral administration of insulin is severely limited by the low bioavailability of insulin through the gastrointestinal tract. In this study, a semi-interpenetrating network gelatin fiber scaffold (sIPN GF) was fabricated for oral mucosal delivery of insulin as an alternative route. This sIPN GF was engineered from an electrospun gelatin fiber scaffold (GF), which was further crosslinked with polyethylene glycol diacrylate (PEG-DA) …

A Novel Device And Nanoparticle-Based Approach For Improving Diagnosis And Treatment Of Pelvic Inflammatory Disease, Natasha Faith Cover

USF Tampa Graduate Theses and Dissertations

Pelvic Inflammatory Disease (PID) is one of the most common causes of morbidity in women. PID is a polymicrobial infection of the female reproductive tract, and is associated with pelvic pain, abnormal uterine bleeding, and tubal damage that can lead to ectopic pregnancies and infertility. It is curable but the effects of PID can be permanent if not properly diagnosed and treated. PID presents as a spectrum of disease and is often missed at early stages; even acute PID can be difficult to diagnose, as there is no single conclusive diagnostic test. Currently, PID is identified and treated syndromically because …

Targeted Multistage Delivery Of Nanoparticles To The Bone Marrow, Aman Mann

Dissertations and Theses (Open Access)

Bone marrow is a target organ site involved in multiple diseases including myeloproliferative disorders and hematologic malignancies and metastases from breast and prostate. Most of these diseases are characterized with poor quality of life, and the treatment options are only palliative due to lack of delivery mechanisms for systemically injected drugs which results in dose limitation to protect the healthy hematopoietic cells. Therefore, there is a critical need to develop effective therapeutic strategies that allow for selective delivery of therapeutic payload to the bone marrow. Nanotechnology-based drug delivery systems provide the opportunity to deliver drugs to the target tissue while …

Nanofabrication Of Halloysite-Pcl Composite Scaffolds And Functionalization Of Titanium For Tissue Regeneration, Shraddha Parshottambhai Patel

Doctoral Dissertations

Major medical needs may be achieved through regenerative medicine. Nanotechnology has triggered a research revolution in many important areas such as the biomedical sciences and bioengineering at the molecular level which has grown significantly due to the availability of new analytical applications and tools based on nanotechnology. Clinical conditions and diseases being targeted by nanotechnology research include burns, Alzheimer's and Parkinson's disease, implant failure, improved wound healing, birth defects, osteoporosis and congestive heart defects. Therapeutic use of growth factors and drugs to stimulate the production and/or function of endogenous cells represents a key area of regenerative medicine. The development of …

Ultrasonic Assisted Layer-By-Layer Assembly For Stable Nanocolloids Of Curcumin And Paclitaxel, Zhiguo Zheng

Doctoral Dissertations

Researchers have been trying to fight cancer with synthesis of new bioactive compounds but many of these novel drugs have low solubility in water and it is difficult to deliver them into a patient's body. One way of solving this particular problem is to use nanoscale drug delivery systems. In this dissertation, we describe using an ultrasonic assisted layer-by-layer encapsulation process to prepare anti-cancer drugs with 50∼200 nm particle size with designed coating to achieve sustained release and target delivery.

Two methods for systematic manufacture of low solubility anti-cancer drug nanoparticles were proposed: I) Top-down approach to breakdown larger drug …

Targeted Nanoparticles For Cancer Therapy: Promises And Challenge, Kytai Truong Nguyen

Bioengineering Faculty Publications - Archive

No abstract provided.

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 …

Synthesis And Characterization Of Novel Temperature-Responsive Dendritic Peg-Pdlla Star Polymers For Drug Delivery, Arunvel Kailasan

Theses and Dissertations

This study describes a novel thermoresponsive dendritic polyethylene glycol-poly(D, L-lactide) (PEG-PDLLA) core-shell nanoparticle with potential for drug delivery and controlled release. A series of dendritic PEG-PDLLA nanoparticles were synthesized through conjugation of PEG to Starburst™ polyamidoamine (PAMAM) dendrimer G3.0 and subsequent ring-opening polymerization of DLLA, in which PEG chain length (i.e., MW=1500, 6000 or 12000 Dalton) was varied; however, the feeding molar ratio of DLLA monomers to the overall PEG repeat units on the dendrimer surface was kept at 1:1. Linear PEG-PDLLA copolymers were also syntheiszed under the same condition and used as control. According to our results, dendritic PEG-PDLLA …

Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran

Doctoral Dissertations

The significance of any drugs, therapeutic proteins, or any bioactive compounds, is based not only on their effects on diseases but also on how specifically, how readily, how controllable and how prolonged their effects on the disease without having any side effects. Thus the techniques involved in the drug encapsulation and its controlled release for a longer duration of time form one of the important processes of drug reformulation. In recent years nanoparticles have created overwhelming attention for delivering drugs by nanoencapsulation. The smaller size of nanoparticles has longer circulation time and higher cellular uptake when compared with larger size …

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.

In Situ Photopolymerized Hydrogels For Enhancing Protein Delivery, Chien-Chi Lin

All Dissertations

In recent years, there has been immense interest in the utilization of photopolymerized hydrogels as carriers for controlled protein delivery and cell scaffolds for tissue engineering applications. Although poly(ethylene glycol) (PEG)-based hydrogels formed from mild photopolymerization methods have been suggested as biocompatible matrices that allow for safely encapsulating biomolecules including proteins, peptides, DNA, and cells, the adverse effects of photopolymerization reactions on the encapsulated proteins have largely been overlooked. In addition, conventional hydrophilic hydrogels fail to effectively control protein delivery rates due to their high permeability. These two problems are critical since the delivery of protein therapeutics from hydrogel matrices …

Effect Of Ventilation Rate On Instilled Surfactant Distribution In The Pulmonary Airways Of Rats, Joseph C. Anderson, Robert C. Molthen, Christopher A. Dawson, Steven Thomas Haworth, Joseph L. Bull, Matthew R. Glucksburg, James B. Grotberg

Biomedical Engineering Faculty Research and Publications

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) …

Interaction Of Liposomal Drug Delivery Systems With Cells And Tissues: Microscopic Studies, M. Foldvari, G. T. Faulkner, C. Mezei, M. Mezei

Cells and Materials

Liposomes , as drug carriers, can be administered into the body by several routes e.g. intravenously, intraperitoneally, intramuscularly, intratracheally and topically among others. Radiolabelled markers are suitable to monitor the distribution and elimination of liposomes, but the tissue deposition of intact liposomes, the mode and sites of drug release from the liposomes and liposome-cell interactions cannot be investigated morphologically. Microscopic techniques could provide information regarding the intact state of liposomes and possibly the dynamics of liposomes in tissues provided that they can be identified with certainty in vivo. This is a formidable problem and in spite of several attempts, there …