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- Creators: Barrett, The Honors College
- Creators: Fauer, Chase Alexander
- Creators: Han, Priscilla
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.
The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and time effectiveness. Theoretical data for the time to 60% drug release and the slope and intercept of the log-log plot were collected and subjected to statistical analysis in JMP. Since the scope of this project focuses on microparticle surface degradation drug release with no drug diffusion, the characteristic variables relating to the slope (n = diffusional release exponent) and the intercept (k = kinetic constant) do not directly apply to the distribution model within the scope of the research. However, these variables are useful for analysis when the Mathcad template is applied to other types of drug release models.
Traumatic brain injury (TBI), a neurological condition that negatively affects neural capabilities, occurs when a blunt trauma impacts the head. Following the initial injury that immediately impacts neural cell function and survival, a series of secondary injury events lead to substantial sustained inflammation for weeks to years post-injury. To develop TBI treatments that may stimulate regenerative processes, a novel drug delivery system that efficiently delivers the appropriate drug/payload to injured tissue is crucial. Hyaluronic acid (HA) hydrogels are attractive when developing a biomaterial for tissue reparation and regeneration. HA is a natural polymer with physicochemical properties that can be tuned to match the properties of the extracellular matrix (ECM) of the many tissues including the central nervous system (CNS). Here, the project objective was to develop a HA hydrogel system for local delivery of a biological payload; this objective was completed by employing a composite system with two parts. The first part is an injectable, shear-thinning bulk hydrogel, and the second is microgels for loading biological payloads. The bulk hydrogel was composed of cyclodextrin modified HA (Cd-HA) and adamantane modified HA (Ad-HA) that give rise to guest-host interactions that facilitate physical crosslinking. The microgel, composed of norbornene-HA (Nor-HA) and sulfated-HA, crosslink via chemical crosslinks upon activation of a UV photoinitiator. The sulfated-HA microgels facilitate loading of biological payloads by mimicking heparin binding sites via the conjugated sulfated group. Neuregulin I, an epidermal growth factor with neuroprotective properties, is one such protein with a heparin binding domain that may be retained in the sulfated-HA microgels. Specifically, the project focused on mechanical testing of this composite microgel/hydrogel system and also developing protein affinity assays.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.