Drug Delivery exam 2020.pdf

1 Technical University of Denmark Written exam, date: 19th August 2020 Page 1 of 8 pages Course name: Drug Delivery Course number: 22235 Aids: All aids allowed Duration: 2 hours Weighting: Question 1 is worth 50 points; Question 2 is worth 50...

1 Technical University of Denmark Written exam, date: 19th August 2020 Page 1 of 8 pages Course name: Drug Delivery Course number: 22235 Aids: All aids allowed Duration: 2 hours Weighting: Question 1 is worth 50 points; Question 2 is worth 50 points. The examinee will answer ALL questions. Name (printed): Student no.: -------------------------------------------------------------------------------------------------------------------------------- Answer all 2 questions. Question 1: Answer all parts Doxorubicin is an intercalating agent widely used as a chemotherapeutic. Doxorubicin can be delivered in either the non-salt or hydrochloride salt form and has the following Log D profile: 2 Using liposomes as the nanocarrier system, design 2 drug delivery systems for doxorubicin: A) A fast acting (i.e. fast release) system for intratumoral injection. B) A slow acting (i.e. slow release) and long circulating system for intravenous injection. Describe each system in as much detail as possible. This should include describing the fundamental science that underpins your design choice, describing the physicochemical properties of the system, describing biological interactions with the system in vivo, and any foreseeable challenges with the system. An example would be to describe the fundamental mechanisms that promote liposome stability both on the bench and in the body. The liposome system can be any size between 50-300 nm, must comprise liposome constituent chemicals and can be chemically functionalized to improve performance. Question 2: Answer all parts Dexamethasone is a corticosteroid that binds to glucocorticoid receptors, which are located in the cell cytosol, suppressing the cell’s inflammatory response. Dexamethasone is widely used in the clinic to treat inflammation associated with changes to endothelial barriers caused by disease. The structure of dexamethasone and 2 dexamethasone prodrugs, dexamethasone 21-hemisuccinate and dexamethasone 21-palmitate (including the Log P values at physiological pH), are shown above. 3 Using polymeric nanoparticles, design 2 drug delivery systems for dexamethasone (dexamethasone prodrugs can also be used): A) A fast acting (i.e. fast release) but short duration anti-inflammatory system which accumulates in inflamed tissues. B) A slow acting (i.e. slow release) but long duration anti-inflammatory system which circulates for prolonged periods in the blood stream. Describe each system in as much detail as possible. This should include describing the fundamental science that underpins your design choice, describing the physicochemical properties of the system, describing biological interactions with the system in vivo, and any foreseeable challenges with the system. An example would be to describe how the molecular weight of the polymer alters polymer chain packing dynamics and polymer degradation. The polymer system can be any size between 50- 500 nm, must comprise polymer constituent chemicals and can be chemically functionalized to improve performance. 4 5 6 7