In vitro, the polymer will break down to poly(ethylene glycol), poly L-lysine)(attached to one molecule of lactic acid at end)and lactic acid, due to hydrolysis of ester bonds in the polymer. The amide bonds are relatively stable under these conditions. In vivo, polylysine will also be degraded to amino acids by the action of proteases and peptidases CH,0 CH2CH20 一NH 2. The generation of acidic or basic degradation products is a serious issue complicating the design of devices for in vivo application, even for well-established materials like poly (lactide Co-glycolide). Propose an approach to limit or eliminate the generation of a low pH within and near a PLGa device implant. Be creative! (limit -1/2 page explanation Many solutions are possible, a few examples Add an acid/base titrating compound(amine monomers) into the material ii. Co-encapsulating lactate dehydrogenase(LDH). LDH will convert lactate into pyruvate-the end product of glycolysis and starting component of Citric acid i. Using salts like Mg(OH)2. The salt being basic will take up all the free protons om lactic acid generation and therefore act as a buffering agent 3. Propose a route to synthesize the hydrolyzable polymer shown below. Show the structure of the monomers you would use and any initiators/catalysts CH3 CH3-c-0-F-CH2-CH2-0-(C-CH-0-C-CH-N)n-H H3 NH As discussed in class, this structure, exactly as drawn, is impossible to synthesize by any common chemical routes. Condensation polymerization of lactic acid and lysine can provide a random arrangement of lactic acid and lysine units in the polymer, but cannot provide a regular repeat-LA- LYS-LA-LYS-LA-LYS-etc. as shown, nor is it straightforward to cap one end of such polymers with a tert-butyl group as shown. The structure that was INTENDEd to be shown is: E4623962JPS1 20f2In vitro, the polymer will break down to poly(ethylene glycol), poly(L-lysine) (attached to one molecule of lactic acid at end) and lactic acid, due to hydrolysis of ester bonds in the polymer. The amide bonds are relatively stable under these conditions. In vivo, polylysine will also be degraded to amino acids by the action of proteases and peptidases. 2. The generation of acidic or basic degradation products is a serious issue complicating the design of devices for in vivo application, even for well-established materials like poly(lactide￾co-glycolide). Propose an approach to limit or eliminate the generation of a low pH within and near a PLGA device implant. Be creative! (limit ~1/2 page explanation). Many solutions are possible, a few examples: i. Add an acid/base titrating compound (amine monomers) into the material ii. Co-encapsulating lactate dehydrogenase (LDH). LDH will convert lactate into pyruvate – the end product of glycolysis and starting component of Citric acid cycle. iii. Using salts like Mg(OH)2. The salt being basic will take up all the free protons from lactic acid generation and therefore act as a buffering agent. 3. Propose a route to synthesize the hydrolyzable polymer shown below. Show the structure of the monomers you would use and any initiators/catalysts. CH3 O O H CH3-C-O-C-CH2-CH2-O-(C-CH-O-C-CH-N)n-H CH3 O CH3 (CH2)4 NH2 As discussed in class, this structure, exactly as drawn, is impossible to synthesize by any common chemical routes. Condensation polymerization of lactic acid and lysine can provide a random arrangement of lactic acid and lysine units in the polymer, but cannot provide a regular repeat –LA￾LYS-LA-LYS-LA-LYS-etc. as shown, nor is it straightforward to cap one end of such polymers with a tert-butyl group as shown. The structure that was INTENDED to be shown is: BE.462J/3.962J PS 1 2 of 2