Combinatorial and High-Throughput Screening of Materials ...

ACS Combinatorial Science
REVIEW
Figure 49. siRNA-DNA materials encapsulated by hydrogels (A) Encapsulation of DNA-siRNA loaded with PEI-PLGA microparticles approach. (B)
Incorporation of hydrogel compents in buffer with microparticles and chemokine. (C) In situ cross-linking of hydrogel. 459
main advantages of hydrogels include unusual high water solubility
and physicochemical properties that can easily be tuned.
Hydrogels are typically porous, making them perfect hosts to
accommodate drug molecules in the gel matrix. On the other
hand, due to this unique property, small molecule drugs can be
delivered by controlled diffusion of the latter to the target site.
Equally, hydrogels can be formulated in a wide range of forms
such as microparticles, nanoparticles and coatings to injectable
materials for drug delivery.
Roy et al. recently reported a microparticle-based system
capable of simultaneously delivering siRNA and DNA to
APCs. 459 The biomaterial is made from PLGA (poly lactic acid
and glycolic acid) and polyvinylalcohol and functionalized polyethylene
imine with encapsulated siRNA-DNA microparticles
(Figure 49A). This system is then further encapsulated with an
in situ dextran or PEG cross-linkable, injectable formulation
containing dendritic cell (DC)-chemo-attractants. The system is
designed as such to attract immature DCs and simultaneously
deliver, to the migrated cells, immunomodulatory siRNA and
plasmid DNA antigens. These low cross-link density hydrogels
were designed to degrade within 2 7 days in vitro and released
chemokines in a sustained manner.
Figure 49B shows the approach in which the si-RNA-DNA
materials from plasmids are integrated into a microparticle which
is then functionalized to a polyethyleneimine microparticle. The
hydrogel is now incorporated alongside with the microparticles.
Cross-linking and formulation of this system will yield the
formation of injectable solutions. A small library of hydrogels
(2 backbones (dextran vinylsulfone vs PEG diacrylate)), various
degree of substitution and gelation times and compositions was
synthesized and characterized using standard characterization
techniques. 436,458
An array of dextran VS and PEGDA hydrogels was made with
and without encapsulated microparticles, (Figure 49C) with
various % of the original monomer and different gelation times
to ensure a high degree of cross-linking. Those materials that
displayed complete gelation were carried forward and further
examined with ELISA, SEM as well as in vitro tests for viability of
these biomaterials in gene delivery. This parallel approach
allowed the rapid identification of promising biomaterials for
gene delivery by just varying the chemical composition, the
degree of cross-linking and the porosity, which all affected the
stability of the hydrogel as well as the release kinetics significantly.
Overall, the studies showed that these novel biomaterials
can deliver genes effectively to the desired sites during the
immunotherapy.
3.5.3. Organic Biomaterials with Cell and Stem Cell Systems.
Understanding interactions between organic or polymeric biomaterials
remains one of the main research directions. Typically
biomaterials that have been designed and made to be used in
regenerative medicine and especially as components used in
body implants have to be tested for biocompatibility and have to
621 dx.doi.org/10.1021/co200007w |ACS Comb. Sci. 2011, 13, 579–633