A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Synthetic Mucus Hydrogels for Antimicrobial Peptide Delivery and Treatment of Bacterial Infections(2024) Yang, Sydney; Duncan, Gregg A; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Antibiotic resistant infections have the propensity to form biofilms that contribute to chronic infections and result in hyper-inflammatory response in tissues. Recent studies pose antimicrobial peptides (AMPs) as alternatives to antibiotics and to modulate inflammatory response. However, AMPs have a short half-life due to rapid clearance and degradation reducing AMP bioavailability and efficacy. In the human body, AMPs interact and may associate with mucins which result in the sequestering of AMPs within mucus. Previously, we have developed a synthetic mucus (SM) hydrogel inspired by the innate properties of mucins. The objective of this work was to evaluate the SM hydrogel as a tool for local antimicrobial peptide delivery of LL37 to enhance the treatment for infection and inflammation. To study this, we (1) assessed the release of LL37 and antimicrobial activity of LL37 loaded SM (LL37-SM) hydrogels on Pseudomonas aeruginosa, (2) evaluated the antibiofilm activity of LL37-SM hydrogel treatment on Pseudomonas aeruginosa biofilms, and (3) determined the impact of LL37-SM hydrogel treatment on RAW 264.7 macrophage activation and phagocytic activity. The association of LL37 to SM hydrogels enabled the sustained release of LL37 over 8 hours and retained antimicrobial activity. Treatment with LL37-SM hydrogels for 24 hours disrupted biofilm growth and resulted in a mixed inflammatory response in macrophages. Our results highlight the antimicrobial, antibiofilm, and potentially inflammatory modulating capabilities of SM hydrogels which can further inform the use of mucins in bioactive biomaterials for biomedical applications.Item Immunological and Toxicological Considerations for the Design of Liposomes(MDPI, 2020-01-22) Inglut, Collin T.; Sorrin, Aaron J.; Kuruppu, Thilinie; Vig, Shruti; Cicalo, Julia; Ahmad, Haroon; Huang, Huang-ChiaoLiposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from the encapsulated therapeutic agent. Decades of research have been dedicated to studying and optimizing liposomal formulations for a variety of medical applications, ranging from cancer therapeutics to analgesics. Some effort has also been made to elucidate the toxicities and immune responses that these drug formulations may elicit. Notably, intravenously injected liposomes can interact with plasma proteins, leading to opsonization, thereby altering the healthy cells they come into contact with during circulation and removal. Additionally, due to the pharmacokinetics of liposomes in circulation, drugs can end up sequestered in organs of the mononuclear phagocyte system, affecting liver and spleen function. Importantly, liposomal agents can also stimulate or suppress the immune system depending on their physiochemical properties, such as size, lipid composition, pegylation, and surface charge. Despite the surge in the clinical use of liposomal agents since 1995, there are still several drawbacks that limit their range of applications. This review presents a focused analysis of these limitations, with an emphasis on toxicity to healthy tissues and unfavorable immune responses, to shed light on key considerations that should be factored into the design and clinical use of liposomal formulations.