Problem Set 2 Model Solutions
100 points total
From the reading for lecture 4 (Kumamoto et al.,
, 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
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.
Suggest an alternative material/release mechanism, and list two advantages and at
least one potential issue with your alternative choice.
Explain the advantages/issues
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