Browsing by Subject "drug delivery"

Now showing 1 - 4 of 4

Embedding of Liquids into Water Soluble Materials via Additive Manufacturing for Timed Release
(University of Texas at Austin, 2017) Zawaski, Callie; Margaretta, Evan; Stevenson, Andre; Pekkanen, Allison; Whittington, Abby; Long, Timothy; Williams, Christopher B.
One fundamental goal of personalized medicine is to provide tailored control of the dissolution rate for an oral dosage pill. Additive manufacturing of oral dose medicine allows for customized dissolution by tailoring both geometric and printed material properties. Direct processing of medicine via filament material extrusion is challenging because many active agents become inactive at the elevated temperatures found in the melt-based process. In this work, this limitation is circumvented by incorporating the active agents via in-situ embedding into a priori designed voids. This concept of embedding active ingredients into printed parts is demonstrated by the in-situ deposition of liquid ingredients into thin-walled, water soluble, printed structures. The authors demonstrate the ability to tune dissolution time by varying the thickness of the printed parts walls using this technique.
Stimuli-Responsive Nanoscale Hydrogels For The Improved Delivery Of Chemotherapeutic Agents
(2019-05-01) Shearer, Alexander; Peppas, Nicholas
Cancer represents one of the largest public health concerns in the world. Current treatment methods for cancer – namely, chemotherapy – possess serious limitations, most notably the nonspecific biodistribution of the cytotoxic drugs, which leads to diminished drug efficacy and undesirable side effects. However, nanomedicines have recently demonstrated great promise in improving the target specificity of chemotherapeutic drugs and thus drug efficacy. Nanomedicines can be designed with ideal properties for drug delivery, and they are able to preferentially accumulate in the diseased site by the enhanced permeability and retention (EPR) effect. However, there are still numerous biological barriers to drug delivery that need to be considered when designing these nanomedicines. In order to overcome these barriers, the nanomedicines or nanoparticles must be rationally designed. By tuning such properties as size, shape, elasticity, hydrophobicity, and surface charge – these nanoparticles can be passively targeted to the diseased site, and even into the cancerous cells. However, it is also beneficial to actively target tumors by functionalizing the particles with target ligands that can preferentially bind to unique or overexpressed receptors or molecules at the tumor site, thereby improving target specificity, as well as facilitating uptake of the nanoparticles by the cell. In the original work of this thesis, the use of pH-sensitive nanogels as drug delivery agents for ovarian cancer was investigated. There were three aims of this investigation: (1) to elucidate the mechanism of internalization in order to determine if endosomal acidification could be leveraged to facilitate cytosolic delivery of the drug payload, (2) to evaluate the effect of stealth coating (PEG) surface density on cellular uptake, (3) and – expecting that the presence of a stealth coating would impede uptake – to design a stimuli responsive peptide linker that would facilitate the shedding of the stealth coating in the presence of a key enzyme that is over expressed in cancer cells – thereby improving uptake. Ultimately, it was determined that the nanogels were internalized via a clathrin-mediated endocytosis process. As a result, these nanogels can, in fact, leverage endosomal acidification to induce nanoparticle swelling, endosomal rupture, and cytosolic delivery. Additionally, particles with no PEG conjugated to the surface exhibited about 90% uptake, but this uptake diminished to about 10% or lower for particles with a PEG content of 10 mol% or higher, showing that the increase in PEG content severely hindered cellular uptake. However, nanoparticles with the enzyme degradable crosslinker that functionalized the PEG to the particle surfaces were successfully synthesized, and it was seen that – in the presence of the enzyme – shedding of the stealth coating was, in fact, observed, and uptake levels returned to those of the particles without PEG coatings. Therefore, it can be concluded that nanogels were rationally designed and successfully synthesized that possessed a multitude of functionalities, each of which contributed to the capacity of the nanogels to delivery drugs to a specific target with a controlled release of the drug payload.
Treating Macrophages with Anti-inflammatory Nanoparticles as a Strategy to Improve Muscle Repair
(2019-05) Yan, Derek; Suggs, Laura
The macrophage is an immune cell that is involved in host defense. More recent research, however, has revealed that they also play a central role in mediating the skeletal muscle regenerative process. Upon muscle injury, macrophages are recruited to the damaged site and begin differentiating into a pro-inflammatory phenotype, known as the M1 phenotype. M1 macrophages secrete inflammatory cytokines to facilitate the acute response to muscle injury, and are characterized by phagocytosis of cellular debris and exhibiting strong microbicidal activity. However, another hallmark of inflammatory macrophages is the metabolism of arginine into nitric oxide (NO), which is further metabolized into other reactive oxygen species such as superoxide and peroxynitrite. If left unchecked, prolonged macrophage inflammation leads to muscle cell lysis due to the persistence of reactive oxygen radicals. The capacity of macrophages to stimulate myogenic cells to proliferate is also reduced if inflammation persists. To improve muscle regeneration, we have developed and synthesized a nanoparticle formulation that allows controlled reduction of macrophage inflammatory phenotype. Previous published studies have shown lactic acid and magnesium as chemical agents that attenuate M1 phenotype in macrophages. We developed a poly-lactic-co-glycolic acid (PLGA) nanoparticle emulsified with magnesium sulfate to attenuate the inflammatory phenotype in a murine macrophage cell line. This Magnesium-PLGA nanoparticle has been optimized to be uptaken by macrophages without affecting cell viability. We hope that these contributions make the first steps towards developing an injectable therapy to modulate macrophage phenotype, and can be used in conjunction with existing treatments to improve skeletal muscle repair following injury.
The Use of Poly(vinyl alcohol)-based Hydrogels in Biomedical Applications
(2018) Subramanian, Deepak; Peppas, Nicholas
Polymers have found increasing favor in biomedical applications due to the greater control that researchers can exert over their properties. Researchers have focused on the development of therapies using biologically compatible polymers due to their ability to limit potentially harmful interactions with the body. This research has led to advances in tissue engineering, controlled and targeted drug delivery, and other biomedical fields, with the goal of improving both the effectiveness and accessibility of health care. Poly(vinyl alcohol) (PVA) hydrogels possess several chemical properties that make them well suited for biomedical applications. These include inertness and stability, biocompatibility, and pH-responsiveness. As a result, PVA based materials have been studied for potential applications in areas of biomedicine such as targeted drug delivery, tissue engineering, and wound healing. This thesis examines the properties of PVA and seeks to understand how the chemical and physical structure affects their properties. It then examines how these properties enhance their utility in potential biomedical applications. Finally, it reviews the research into development of PVA based materials for three different biomedical applications.