Liposomes are self-assembled lipid vesicles made from phospholipids that are safe and suitable for drug encapsulation and localized drug delivery. Liposomal formulations are characterized by low toxicity and improved therapeutic index (by changing drug biodistribution) and liposomes encapsulating antifungal or anticancer drugs have already been approvedby regulatory agencies.One area of application for liposomes is localized antibiotic delivery. Antibiotics target bacteria, but specific types of infections(namely biofilms or intracellular infections)that required high or prolonged antibiotic administration have long been a challenge for antibiotic treatments. Liposomal delivery of antibiotics can improve their therapeutic index while minimizing their adverse effects. When it comes to methods of antibiotic encapsulation, however,most reports to date follow the methods developed for anticancer drugs for encapsulating antibiotics. This oversight causes discrepancies in the literature, mainly because of the significantly different chemical structures of antibiotics and cancer drugs. Furthermore, most antibiotics are highly sensitive to temperature fluctuations, which is concerning, given most liposomal preparation methods involve extreme temperature fluctuations. The aim of my thesis was to explore these missing links in the literature by answering these questions: (1) will liposome preparation method affect encapsulation efficiency of antibiotics?And (2) does liposomal preparation method adversely affect the efficacy of antibiotics?Investigating these questions led to further insight into the optimal process for achieving high encapsulation efficiencies for different antibiotics and for further avoiding damage due to harsh processing conditions. We found that different preparation methods are better for different types of antibiotics, being the one that promotes a large aqueous space better for hydrophilic drugs and the one that creates oligolamellar and large unilamellar vesicles better for more hydrophobic drugs. The steps in liposome preparation methods such as heating and sonication can affect the stability of the antibiotics. / Thesis / Master of Applied Science (MASc) / When antibiotics are administered, orally or intravenously, they should pass through different tissues to arrive to the site of infection; this can cause dilution and/or intoxication. To overcome these problems, drug delivery vehicles have been used to encapsulate and deliver antibiotics, improving their therapeutic index while minimizing their adverse effects. Liposomes are vesicles composed of at least one lipid bilayer, with an inner aqueous compartment. Liposomes are an attractive vehicle to deliver antibiotics because they can encapsulate both hydrophobic and hydrophilic antibiotics, they have low toxicity, and they can change the bio-distribution of the drug. In mythesis, I addressedtwo main questions regarding liposomal antibiotic encapsulation:(1) will liposome preparation method affect encapsulation efficiency of antibiotics, and(2) does liposome preparation method adversely affect the efficacy of antibiotics. While investigating these questions,I also identified certain outstanding biases in the liposomal characterization methods.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23803 |
| Date | January 2019 |
| Creators | González Gómez, Azucena |
| Contributors | Hosseini-Doust, Zeinab, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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