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Browsing by Subject "cancer therapeutics"

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  • Karumo, Suvi (2022)
    Liposomes are biocompatible spherical nanosized vesicles consisting of hydrophobic phospholipid bilayer encasing an aqueous core. They can be utilized as drug carriers by either encapsulating molecules inside the core or embedding them in the bilayer accordingly to achieve numerous advantages such as prevention of rapid clearance and reduction of adverse effects as systemic exposure is reduced. Despite the marked efforts in designing the liposomes to improve therapeutic outcomes, only limited drug concentrations are achieved at the target sites such as in solid tumors. Stimuli-responsive liposomes could be applied as potential delivery systems to achieve spatiotemporally controlled drug delivery, i.e., the drug release could be pinpointed and restrained to the target site. In this thesis, the objective was to study the light-activated indocyanine green (ICG) liposomes as nanocarriers for peptide-based anti-tumor agents. The physicochemical characteristics, stability and functionality of the prepared liposomes were determined alongside optimizing the formulation as needed and utilizing different model peptides as encapsulated compounds. Additionally, the peptide stability during near-infrared (NIR) light illumination and the effects of the anti-angiogenic model peptides in vitro were investigated. The stability of the liposomes was assessed by monitoring the size of the liposomes, intactness of ICG, and passive leakage of the peptides over time, and by determining the phase transition temperatures of the different formulations. The liposomes remained adequately stable in different relevant conditions, and the observed phase transition temperatures did not indicate the lipid bilayer becoming permeable in physiological temperatures. However, the rate of passive leakage was rather high in all formulations, although with stiffer lipid bilayer in the “rigid” formulation, the unintended release was able to be decreased slightly in comparison to the other formulations. On the other hand, light-triggered release upon illuminating the liposomes remained considerably low in all formulations. The intactness of peptides seemed to not be impacted by the illumination. Also, no cytotoxic effects were observed after exposing human umbilical vein endothelial cells (HUVEC) to the peptides. The final “rigid” formulation showed the best functionality out of those included in the studies. It remains to be investigated whether the formulation could be improved further for optimal functionality and stability, and to what degree do the properties of the cargo molecule affect the performance of the liposomes.