Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies
Acne vulgaris and atopic dermatitis are the world’s most common skin diseases. Both are associated with the overgrowth of Cutibacterium acnes bacteria (formerly known as Propionibacterium acnes) for the first one and Staphylococcus aureus for the second. While direct inhibition of C. acnes and S. au...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2021
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/145963 |
| _version_ | 1811688027998650368 |
|---|---|
| author | Valle González, Elba Ruth |
| author2 | Cho Nam-Joon |
| author_facet | Cho Nam-Joon Valle González, Elba Ruth |
| author_sort | Valle González, Elba Ruth |
| collection | NTU |
| description | Acne vulgaris and atopic dermatitis are the world’s most common skin diseases. Both are associated with the overgrowth of Cutibacterium acnes bacteria (formerly known as Propionibacterium acnes) for the first one and Staphylococcus aureus for the second. While direct inhibition of C. acnes and S. aureus can improve therapeutic outcomes, this goal is difficult to achieve due to the growing rise of antibiotic-resistant strains and current therapies rely mainly on ameliorating disease symptoms. Improved treatment strategies are needed to directly inhibit C. acnes and S. aureus, and mitigate disease symptoms. One promising bioinspired option involves utilizing natural antimicrobial lipids and glycolic acid. Antimicrobial lipids are found in the epidermis and are designed to protect against undesired bacteria and regulate the microbiome. Glycolic acid is a well-known compound in skincare used to diminish wrinkles and marks. To further improve the cutaneous delivery of the formulation with antimicrobial lipids, bicelles were devised. Bicelles are a new type of nanocarriers that have proved to be effective in dermal uptakes by guaranteeing the local effect, skin appendage penetration and time controlled delivery. The overall hypothesis of this thesis was that the therapeutic activities of the antimicrobial lipids assembled as bicelles and glycolic acid can be employed in additive multifunctional combination to treat C. acnes and S. aureus infections. To test the hypothesis, an integrated combination of chemical, physical and biological experimental approaches were undertaken. First the antibacterial effect of antimicrobial lipids, namely lauric acid and glycerol monolaurate, was characterized by employing model membrane platforms and establishing correlations with antibacterial activity. Secondly, the anti-infective activity of glycolic acid against C. acnes was evaluated. The mechanism by which glycolic acid destroys the cell membrane was determined using a fluorescent counterstaining technique to distinguish live and dead cells, and by monitoring a sensitive marker for membrane damage. Third, bicelles were developed for the protection, delivery and effect enhancement of the antimicrobial lipid on skin. The bicelles size was resolved with light scattering and electron microscopy to match it with the antimicrobial activity. Finally, the cell proliferation and viability were tested over human immortalized keratinocyte cells (HaCaT) to prove its safeness. Taken together these outcomes, it was proven that glycerol monolaurate and glycolic acid are a viable and feasible solution to treat C. acnes and S. aureus infections. It provide mechanistic insight into how antimicrobial lipids, glycolic acid and bicelles with glycerol monolaurate operate and destroy bacterial membranes under skin-relevant environmental conditions. |
| first_indexed | 2024-10-01T05:25:41Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/145963 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:25:41Z |
| publishDate | 2021 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1459632023-03-04T16:38:47Z Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies Valle González, Elba Ruth Cho Nam-Joon School of Materials Science and Engineering NJCho@ntu.edu.sg Engineering::Materials Acne vulgaris and atopic dermatitis are the world’s most common skin diseases. Both are associated with the overgrowth of Cutibacterium acnes bacteria (formerly known as Propionibacterium acnes) for the first one and Staphylococcus aureus for the second. While direct inhibition of C. acnes and S. aureus can improve therapeutic outcomes, this goal is difficult to achieve due to the growing rise of antibiotic-resistant strains and current therapies rely mainly on ameliorating disease symptoms. Improved treatment strategies are needed to directly inhibit C. acnes and S. aureus, and mitigate disease symptoms. One promising bioinspired option involves utilizing natural antimicrobial lipids and glycolic acid. Antimicrobial lipids are found in the epidermis and are designed to protect against undesired bacteria and regulate the microbiome. Glycolic acid is a well-known compound in skincare used to diminish wrinkles and marks. To further improve the cutaneous delivery of the formulation with antimicrobial lipids, bicelles were devised. Bicelles are a new type of nanocarriers that have proved to be effective in dermal uptakes by guaranteeing the local effect, skin appendage penetration and time controlled delivery. The overall hypothesis of this thesis was that the therapeutic activities of the antimicrobial lipids assembled as bicelles and glycolic acid can be employed in additive multifunctional combination to treat C. acnes and S. aureus infections. To test the hypothesis, an integrated combination of chemical, physical and biological experimental approaches were undertaken. First the antibacterial effect of antimicrobial lipids, namely lauric acid and glycerol monolaurate, was characterized by employing model membrane platforms and establishing correlations with antibacterial activity. Secondly, the anti-infective activity of glycolic acid against C. acnes was evaluated. The mechanism by which glycolic acid destroys the cell membrane was determined using a fluorescent counterstaining technique to distinguish live and dead cells, and by monitoring a sensitive marker for membrane damage. Third, bicelles were developed for the protection, delivery and effect enhancement of the antimicrobial lipid on skin. The bicelles size was resolved with light scattering and electron microscopy to match it with the antimicrobial activity. Finally, the cell proliferation and viability were tested over human immortalized keratinocyte cells (HaCaT) to prove its safeness. Taken together these outcomes, it was proven that glycerol monolaurate and glycolic acid are a viable and feasible solution to treat C. acnes and S. aureus infections. It provide mechanistic insight into how antimicrobial lipids, glycolic acid and bicelles with glycerol monolaurate operate and destroy bacterial membranes under skin-relevant environmental conditions. Doctor of Philosophy 2021-01-18T08:17:29Z 2021-01-18T08:17:29Z 2020 Thesis-Doctor of Philosophy Valle-González, E. R. (2020). Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/145963 10.32657/10356/145963 en 10.1021/acs.langmuir.8b02536 10.1038/s41598-020-64545-9 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Engineering::Materials Valle González, Elba Ruth Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title | Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title_full | Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title_fullStr | Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title_full_unstemmed | Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title_short | Biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| title_sort | biophysical characterization of natural antimicrobials towards development of antibacterial skin therapies |
| topic | Engineering::Materials |
| url | https://hdl.handle.net/10356/145963 |
| work_keys_str_mv | AT vallegonzalezelbaruth biophysicalcharacterizationofnaturalantimicrobialstowardsdevelopmentofantibacterialskintherapies |