Synthesis, Characterization and Performance of Gelatin Biopolymer based Nanoparticle Formulations for Molecule Encapsulations
Stevenson Jr, Andre Terrance
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Gelatin's ability to dissolve in water while also forming a gel upon cooling, produces melt in your mouth candies and frozen desserts, along with hard and soft capsules and tablets. This protein, which is extracted from pork skin and cattle hide, is categorized by a rigidity or stiffness value and remains one of the most common materials in food and pharmaceutical formulations. Its established use and safe certification are appealing characteristics for manipulation into nanoparticles (NPs) to encapsulate therapeutic molecules as medicine. NPs are generally spherical materials, yet their abilities hold great promise to improve medical outcomes. These abilities include: protecting molecules from harsh locations like the stomach, improved therapeutic delivery through biological barriers such as the brain and controlled release for minimal side effects. NPs typically less than 200 nanometers (nm) overcome biological barriers more effectively than larger particles. For reference, 200 nm is equivalent to dividing the length of an ant (~4 millimeters) by 20,000. The potential applications of gelatin NPs to treat disease is impressive; however, an inability to consistently obtain ideal NP sizes (<200 nm average diameter) exists. Furthermore, gelatin NPs are commonly stabilized (or cross-linked) using toxic chemicals. The motivation for this research was to (1) contribute new understanding why ideal gelatin NPs are difficult to obtain and (2) form NPs using a non-toxic chemical for prospective brain injury treatment. This dissertation determined low rigid and high rigid gelatin can consistently form NPs less than 200 nm, indicating rigidity alone is not a main factor for obtaining ideal NPs. Instead, characterization approaches indicated gelatin sample composition prior to NP formation must be very uniform. As a result, filtering solutions prior to NP formation proved a new technique to prepare ideal NPs. Glyceraldehyde is a sugar and has shown to be a non-toxic gelatin NP stabilizer. For the first time, glyceraldehyde's non-toxicity was shown using various brain cell types and NPs were formed to be ~130 nm. After incorporation of a new therapeutic molecule for brain injury treatment, average particles were ~149 nm with slow therapeutic release profiles determined in simulated body fluid.
- Doctoral Dissertations