Problem set 1 BE462J3.962J Biodegradable Solid Polymers Spring 2003 Issued Day 1 Day 3 1. The chemical structure of a new degradable polymer, poly (ethylene glycol)-b-polylysine-b- poly (D, L-lactide), is shown below a. Based on chemical structure alone, discuss your prediction of whether this material will degrade more quickly or more slowly than poly (L-lactide)in vivo b. Cite 2 physical data you would want to know to make a better prediction in part (a) and explain why these would aid in this estimate C. What will the end-point degradation products of this polymer be if it is degraded by incubation in vitro in phosphate buffered saline, pH 7. 4 at 37C? Would these products be different if the material were degraded in vivo? 2H20 C-CH 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) E4623962JPS1
Problem Set 1 BE.462J/3.962J Biodegradable Solid Polymers Spring 2003 Issued: Day 1 Due: Day 3 1. The chemical structure of a new degradable polymer, poly(ethylene glycol)-b-polylysine-bpoly(D,L-lactide), is shown below. a. Based on chemical structure alone, discuss your prediction of whether this material will degrade more quickly or more slowly than poly(L-lactide) in vivo. b. Cite 2 physical data you would want to know to make a better prediction in part (a), and explain why these would aid in this estimate. c. What will the end-point degradation products of this polymer be if it is degraded by incubation in vitro in phosphate buffered saline, pH 7.4 at 37°C? Would these products be different if the material were degraded in vivo? 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(lactideco-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). BE.462J/3.962J PS 1 1 of 1
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-O-(C-CH-O-C-CH-N)M-H CH3 O NH 4. In order to carry out studies of polymer hydrolysis on reasonable experimental timescales, a number of researchers have used elevated temperature to speed up degradation. Using the data given below, determine the degradation mechanism (surface or bulk erosion) for a sample of polycaprolactone (p=1. 146 g/cm)0.02m thick degraded in water at 37C and whether the mechanism is changed by degrading the sample at 85.(Hint: assume both the hydrolysis rate constant and the diffusivity of water in the polymer have an Arrhenius form At37°C:k=9.7×103s1 0°cms At50°C:k=5.4×107s1 5×103cm k= rate constant of PCL bond hydrolysis DH20=diffusivity of water in PCL E4623962JPS1 20f2
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 4. In order to carry out studies of polymer hydrolysis on reasonable experimental timescales, a number of researchers have used elevated temperature to speed up degradation. Using the data given below, determine the degradation mechanism (surface or bulk erosion) for a sample of polycaprolactone (ρ = 1.146 g/cm3 ) 0.02m thick degraded in water at 37°C and whether the mechanism is changed by degrading the sample at 85°. (Hint: assume both the hydrolysis rate constant and the diffusivity of water in the polymer have an Arrhenius form.) At 37°C: k = 9.7x10-8 s-1 DH2O = 10-8 cm2 s-1 At 50°C: k = 5.4x10-7 s-1 DH2O = 3.5x10-8 cm2 s-1 k = rate constant of PCL bond hydrolysis DH2O = diffusivity of water in PCL BE.462J/3.962J PS 1 2 of 2
