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Nanoforms of cabozantinib - preparation and characterisation
Fürbacherová, Pavlína ; Indra, Radek (advisor) ; Mrízová, Iveta (referee)
Cancer diseases belong among most serious problems of modern medicine, after cardiovascular problems. In connection with finding the solution of this problem, in recent years there was a development of so-called targeted therapy, which uses nanoparticles in the treatment, which are supposed to make the treatment more effective. One of nanoparticles used in the targeted therapy, is apoferritin, which is naturally occurring transport and storage protein in the human body. Apoferritin has a cavity in its structure, into which a cytostatic agent can be incorporated. In addition, its structure is strongly dependent on the pH value, which makes the incorporation and the subsequent release of the drug in the desired location easily impressionable. These properties make apoferritin a suitable potential nanotransporter. The drug studied in this thesis is the cytostatic drug called cabozantinib. It's tyrosinkinase inhibitor, used in the treatment of advanced metastatic medullary thyroid carcinoma, hepatocellular carcinoma and refractory renal carcinoma. In this thesis, the preparation of cabozantinib complex incorporated in apoferritin was optimized, and subsequently the release of the drug from apoferritin and the metabolism of this complex were monitored using liver microsomes and cytochromes. The results...
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Preparation of anticancer drugs bound in apoferritin
Fürbacherová, Pavlína ; Indra, Radek (advisor) ; Koblihová, Jitka (referee)
Cancer is one of the most serious problems, which modern medicine faces. In recent years, nanotechnologies and their use in medicine, has developed greatly. The aim is to make drug administration more effective and help to improve treatment of cancer illnesses. Incorporation of chemical substance into a nanoparticle can solve the problem with low stability of the drug, and/or it help to eliminate side effects. Nanoparticle apoferritin, which was studied in this thesis, is a form of commonly occurring protein ferritin. Its structure contains cavity, that can be used for incorporation of drug. Its chemical structure (high temperature stability and stability at wide pH range, easy manipulation by changing pH) and its biocompatibility makes apoferritin a potentionally suitable transporter. Presented thesis studied apoferritin's ability to incorporate anticancer drug cabozantinib into its structure. Cabozantinib is tyrosine kinase inhibitor which is used for treatment of thyroid cancer, renal cell carcinoma and hepatocellular carcinoma. The effect of final pH to the formation of the complex of apoferritin with cabozantinib, and stability of this complex was also studied in this thesis. Considering the results we can say that apoferritin is able to encapsulate cabozantinib into its inner structure. As we...
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