pset2_solns - Problem Set 2 Model Solutions Issued:...

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Problem Set 2 Model Solutions 20.462J/3.962J Issued: 02/23/06 Spring 2006 Due: 03/02/06 100 points total 1. From the reading for lecture 4 (Kumamoto et al., Nat. Biotech . 20 , 64-69 (2002)), we saw an example of how controlled release materials can be applied to create vaccines that attract immune cells to an immunization site. In this study, poly(ethylene-co-vinyl acetate) matrices were used. These are prepared by loading the polymer with a high amount of protein, such that the phase-separated protein forms a percolating network through the matrix, allowing for diffusion of the protein out of the sample once it is hydrated; as discussed in class, this leads to diffusion-based release much like a standard nondegradable matrix-based diffusion release. a. Based on your reading/analysis of the paper, cite what you think are the two most important limitations of the chosen matrix material for the given application, and explain your choices. Probably the most important limitation of the strategy in this paper is the use of a nondegradable material for the vaccine—hence this approach requires recovery of the matrix at the end of its useful lifetime (which is very short). Because the material would be need to be retrieved, this also necessitates the use of a non-injectable form that is recoverable (e.g., the millirods used in this study). A second issue relates to the achievable timespan of antigen/chemokine delivery achievable by the poly(ethylene-co-vinyl acetate): diffusion of protein from this matrix is quite rapid, completing over the course of ~48 hrs, and thus, amplifying the immune response further by more sustained antigen delivery/chemoattraction is not possible with this matrix. b. Suggest an alternative material/release mechanism, and list two advantages and at least one potential issue with your alternative choice. Explain the advantages/issues you identify. A second simple approach, just as one example, could be to co-encapsulate chemokine and antigen within degradable microspheres, for example poly(lactide-co-glycolide) (or any one of numerous other materials we have discussed). These would provide an injectable, resorbable source for delivery, would co-localize the chemoattraction and antigen delivery centers, and, by using a slow-eroding material such as a polyester, release could be sustained for weeks. As we discussed in class, a potential limitation of this alternative approach could be
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This note was uploaded on 11/11/2011 for the course BIO 20.410j taught by Professor Rogerd.kamm during the Spring '03 term at MIT.

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pset2_solns - Problem Set 2 Model Solutions Issued:...

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