Chemical and Biomolecular Engineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2751
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Item Biomimetic Polymer Capsules: Novel Architecture and Properties(2021) Ahn, So Hyun; Raghavan, Srinivasa R.; Bentley, William E.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This study focuses on polymer capsules made from biocompatible, water-soluble polymers. Typically, the capsule core is a hydrogel in which proteins, nanoparticles, or biological cells can be encapsulated, while the capsule shell is permeable to small, but not large molecules. We explore two new designs or architectures for such capsules. One is a multi-compartment capsule (MCC) where a capsule has several distinct compartments inside it. A second design is a multilayer capsule, where concentric layers of different chemistries surround a core. These new designs mimic structures commonly found in nature such as a eukaryotic cell or an onion. Our goal is to exploit these novel capsule architectures to achieve new or improved properties. In our first study, we introduce a new kind of multilayer capsule, wherein a protective shell of covalently crosslinked polymer (acrylate) surrounds a core formed by physical crosslinking (alginate). Alginate capsules are widely used for cell-encapsulation, but they are quite weak. We show that a covalent acrylate shell can be added to these capsules in a single step under mild conditions. The shell protects the core from degradation while allowing the encapsulated cells to remain viable and functional. A variation of the synthesis technique yields capsules with two concentric shells (alginate, then acrylate) surrounding a liquid core. Next, we create MCCs in which microbes from two different kingdoms, i.e., bacteria (Pseudomonas aeruginosa) and fungi (Candida albicans), are placed next to each other in distinct inner compartments. This MCC platform holds advantages over traditional co-culture as it eliminates physical contact between the two microbes and allows for real-time monitoring of cell growth in 3D. Using this platform, we study the effects of both physical variables (e.g., pH) as well as chemical additives (e.g., surfactants) on the growth of the two populations. We also detect crosstalk between the bacteria and fungi, i.e., as the bacteria grow, they inhibit the formation of hyphal filaments by the fungi, which make the fungi less invasive. Lastly, we create MCCs with ‘smart’ inner compartments, which are sensitive to various stimuli. An analogy is drawn to different organelles in a cell, which have different constituents and unique functions. We select the chemistry or architecture of each inner compartment of the MCC such that their responses are distinct and orthogonal. For example, one compartment alone breaks apart when the MCC is contacted with an enzyme, while another gets degraded by the introduction of hydrogen peroxide (H2O2), and a third is disrupted by ultraviolet (UV) light. Another concept is shown where the degradation of one compartment induces the degradation of another. We believe these new designs will make the MCC platform more attractive for various biological applications.Item Therapeutic contact lenses for extended drug delivery(2021) Torres Luna, Cesar Eduardo; Wang, Nam Sun; Briber, Robert M; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)There is significant interest in hydrogel-based drug-eluting contact lenses as platforms for topical ocular drug delivery. These devices have shown to provide an increased residence time of drugs at the surface of the eye, leading to enhanced bioavailability (~ 50%) when compared to eye drops (1–5%). One major limitation of contact lenses for drug delivery is that most drugs are released in a few hours, which limits their application for extended delivery. In this dissertation, we develop novel drug-eluting contact lenses that are capable of achieving extended in vitro drug delivery. In our first study, we describe the application of drug-participating catanionic aggregates in poly-(2-hydroxy-ethyl-methacrylate) based contact lenses. Contact lenses embedded with catanionic aggregates can achieve extended delivery of at least 1-week for two anionic drugs. Release kinetics is significantly dependent on the drug’s octanol-water partition coefficient, the hydrocarbon chain length and concentration of the cationic surfactant. Next, we focus on the use of unsaturated fatty acids in commercial contact lenses to extend the release of three cationic drugs. We demonstrate that lenses loaded with oleic acid can extend drug release kinetics to over 1 month. An opposite effect is seen for two anionic drugs, where oleic acid significantly accelerates release kinetics. These studies confirm the dominating impact of coupling charge interactions between drug molecules and fatty acid carrier molecules in contact lenses to adjust drug delivery rates. Finally, we extend the application of fatty acids in contact lenses to evaluate the effect of hydrocarbon chain length, ionic strength, and pH on the release kinetics. It is shown that fatty acids with carbon chain lengths equal or greater than 12 are capable of extending drug release of two cationic drugs, which confirms the importance of hydrophobic interactions with the silicone domain of the gel matrix. By decreasing ionic strength (from 1665 to 167 mM) or increasing the pH of the release media (from 5.5 to 7.4), release kinetics is significantly extended. In summary, the use of fatty acids to control the release of oppositely charged drug molecules represents a versatile tool to modify contact lenses for drug delivery applications.