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%.

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.

Alginate microspheres have recently become increasingly popular in the realm of drug delivery for their biocompatibility, nontoxicity, inexpensiveness, among other factors. Recent strict regulations on microsphere size have drastically increased manufacturing cost and waste, even though the effect of size variance on drug delivery and subsequent performance is unclear. If sphere size variance does not significantly affect drug release profiles, it is possible that future ordinances may loosen tolerances in manufacturing to limit waste produced and expenditures. We use a mathematical model developed by Nickel et al. [12], to theoretically predict drug delivery profiles based on sphere size, and correlate the expected release with experimental data. This model considers diffusion as the key component for drug delivery, which is defined by Fick’s Laws of Diffusion. Alginate, chosen for its simple fabrication method and biocompatibility, was formed into microspheres with a modified extrusion technique and characterized by size. Size variance was introduced in batches and delivery patterns were compared to control groups of identical size. Release patterns for brilliant blue dye, the mock drug chosen, were examined for both groups via UV spectrometry. The absorbance values were then converted to concentration value using a calibration curve done prior to experimentation. The concentration values were then converted to mass values. These values then produced curves representing the mass of the drug released over time. Although the control and experimental values were statistically significantly different, the curves were rather similar to each other. However, when compared to the predicted release pattern, the curves were not the same. Unexpected degradation caused this dissimilarity between the curves. The predictive model was then adjusted to account for degradation by changing the diffusion coefficient in the code to a reciprocal first order exponent. The similarity between the control and experimental curves can insinuate the notion that size tolerances for microsphere production can be somewhat lenient, as a batch containing fifteen beads of the same size and one with three different sizes yields similar release patterns.