Smart delivery systems for cancer treatment using advanced liposome formulations: fabrication, spectroscopic characterization and cell internalization studies
Ozolina, Rasa (2016)
Ozolina, Rasa
2016
Master's Degree Programme in Electrical Engineering
Tieto- ja sähkötekniikan tiedekunta - Faculty of Computing and Electrical Engineering
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Hyväksymispäivämäärä
2016-06-08
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201605264177
https://urn.fi/URN:NBN:fi:tty-201605264177
Tiivistelmä
Cancer is a leading cause of death in the world; consequently, an increasing number of studies have been dedicated to the improvement of cancer therapy treatments over several decades.
The objective of this thesis is to fabricate anti-cancer liposomal formulation, with a novel, improved composition, consisting of lipid vesicles encapsulating anti-cancer drug doxorubicin (DOX) and to spectroscopically characterize these liposomes. In addition, the internalization process of the drug in cells was studied by using advanced fluorescence imaging techniques.
DOX is used for wide variety of cancer types but its main disadvantage is high toxicity for other healthy organs and tissues that can lead to fatal complications. The use of liposomes as carriers of DOX is thus very appealing to counteract this disadvantage and protect the healthy tissues from contact with the DOX toxicity. A number of DOX liposomal formulations using active loading methods have been developed. With these loading methods large amounts of DOX are encapsulated and lead to the formation of dimers, lowering drug activity.
In this work a carrier system made of Dioctadecyldimethylammonium Bromide (DO-DAB) and 1-oleoyl-rac-glycerol (Monoolein (MO)) with a ratio of (1:2) is proposed. This system has recently been described to have the potential of encapsulating drugs, not only at the DODAB enriched bilayer level, but also at the inverted non-lamellar MO-enriched phases at the vesicle interior.
After fabrication the stability of the liposomal system was tested by measuring the size and zeta potential of the liposomes. Four different ‘nano-ruler’ n-(9-anthroyloxy)-stearic acid (n-AS) probes at 3rd, 6th, 9th and 12th – carbon positions of an membrane inserted lipid chain were used for determination of the nanoscale localization of DOX inside the liposome bilayer. These studies revealed that DOX is located closest to the 9-AS probe, close to the bilayer center. The internalization of the liposomal formulation in epidermoid and lung carcinoma cells was analyzed using confocal imaging. It was concluded that the formulation with DOX encapsulated in DODAB:MO (1:2) has more controlled drug release compared to the free drug and a commercial formulation, confirming the potential of the developed formulation for cancer treatment.
The objective of this thesis is to fabricate anti-cancer liposomal formulation, with a novel, improved composition, consisting of lipid vesicles encapsulating anti-cancer drug doxorubicin (DOX) and to spectroscopically characterize these liposomes. In addition, the internalization process of the drug in cells was studied by using advanced fluorescence imaging techniques.
DOX is used for wide variety of cancer types but its main disadvantage is high toxicity for other healthy organs and tissues that can lead to fatal complications. The use of liposomes as carriers of DOX is thus very appealing to counteract this disadvantage and protect the healthy tissues from contact with the DOX toxicity. A number of DOX liposomal formulations using active loading methods have been developed. With these loading methods large amounts of DOX are encapsulated and lead to the formation of dimers, lowering drug activity.
In this work a carrier system made of Dioctadecyldimethylammonium Bromide (DO-DAB) and 1-oleoyl-rac-glycerol (Monoolein (MO)) with a ratio of (1:2) is proposed. This system has recently been described to have the potential of encapsulating drugs, not only at the DODAB enriched bilayer level, but also at the inverted non-lamellar MO-enriched phases at the vesicle interior.
After fabrication the stability of the liposomal system was tested by measuring the size and zeta potential of the liposomes. Four different ‘nano-ruler’ n-(9-anthroyloxy)-stearic acid (n-AS) probes at 3rd, 6th, 9th and 12th – carbon positions of an membrane inserted lipid chain were used for determination of the nanoscale localization of DOX inside the liposome bilayer. These studies revealed that DOX is located closest to the 9-AS probe, close to the bilayer center. The internalization of the liposomal formulation in epidermoid and lung carcinoma cells was analyzed using confocal imaging. It was concluded that the formulation with DOX encapsulated in DODAB:MO (1:2) has more controlled drug release compared to the free drug and a commercial formulation, confirming the potential of the developed formulation for cancer treatment.