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- All Subjects: Microparticles
- All Subjects: TBI
- Creators: Stabenfeldt, Sarah
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) is defined as an injury to the head that disrupts normal brain function. TBI has been described as a disease process that can lead to an increased risk for developing chronic neurodegenerative diseases, like frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A pathological hallmark of FTLD and a hallmark of ALS is the nuclear mislocalization of TAR DNA Binding Protein 43 (TDP-43). This project aims to explore neurodegenerative effects of TBI on cortical lesion area using immunohistochemical markers of TDP-43 proteinopathies. We analyzed the total percent of NEUN positive cells displaying TDP-43 nuclear mislocalization. We found that the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was significantly higher in cortical tissue following TBI when compared to the age-matched control brains. The cortical lesion area was analyzed for each injured brain sample, with respect to days post-injury (DPI), and it was found that there were no statistically significant differences between cortical lesion areas across time points. The percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was analyzed for each cortical tissue sample, with respect to cortical lesion area, and it was found that there were no statistically significant differences between the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization, with respect to cortical lesion area. In conclusion, we found no correlation between the percent of cortical NEUN positive cells displaying TDP-43 nuclear mislocalization with respect to the size of the cortical lesion area.
Annually approximately 1.5 million Americans suffer from a traumatic brain injury (TBI) increasing the risk of developing a further neurological complication later in life [1-3]. The molecular drivers of the subsequent ensuing pathologies after the initial injury event are vast and include signaling processes that may contribute to neurodegenerative diseases such as Alzheimer’s Disease (AD). One such molecular signaling pathway that may link TBI to AD is necroptosis. Necroptosis is an atypical mode of cell death compared with traditional apoptosis, both of which have been demonstrated to be present post-TBI [4-6]. Necroptosis is initiated by tissue necrosis factor (TNF) signaling through the RIPK1/RIPK3/MLKL pathway, leading to cell failure and subsequent death. Prior studies in rodent TBI models report necroptotic activity acutely after injury, within 48 hours. Here, the study objective was to recapitulate prior data and characterize MLKL and RIPK1 cortical expression post-TBI with our lab’s controlled cortical impact mouse model. Using standard immunohistochemistry approaches, it was determined that the tissue sections acquired by prior lab members were of poor quality to conduct robust MLKL and RIPK1 immunostaining assessment. Therefore, the thesis focused on presenting the staining method completed. The discussion also expanded on expected results from these studies regarding the spatial distribution necroptotic signaling in this TBI model.