Table 4. Silk Stabilization of Small Molecules.

Small Molecule Immobilized	Silk Immobilization Approach	Key Stabilization Results	Reference
Adenosine	Drug encapsulated into silk microspheres, loaded into silk sponges and coated with drug-loaded silk films	Duration of sustained in vitro adenosine release corresponded to duration of in vivo therapeutic effect (seizure suppression in a kindled rat model of epilepsy) Bioactivity of adenosine encapsulated in silk preserved in vivo up to 10 days	Wilz et al., 2008; Szybala et al., 2009
Chlorophyll a β-carotene Astaxanthin	Adsorption onto silk powder	Silk-pigment conjugates exhibited high UV light stability, while free pigments decolorized rapidly when exposed to UV light	Ishii et al., 1995
Antioxidants from crude olive leaf extract (oleuropein and rutin)	Adsorption onto silk powder	Functionalized silk fibroin exhibited antioxidative and antimicrobial activity Antioxidant activity of desorbed polyphenols following adsorption to silk nearly doubled compared to crude extract	Bayçin et al., 2010
Doxycycline Ciprofloxacin	Adsorption onto silk fibers	Functionalized silk fibers repressed local bacterial lawn growth for at least 48 hours (doxycycline) or 24 hours (ciprofloxacin)	Choi et al., 2004
Curcumin	Encapsulated in silk nanoparticles	Bioactivity preserved during encapsulation Curcumin in silk nanoparticles reduced viability of breast cancer cells in vitro	Gupta et al., 2009
Various antibiotics (penicillin, tetracycline, rifampicin, erythromycin)	Various immobilization approaches, including bulk loading, adsorption and encapsulation	Storage of penicillin and tetracycline in bulk-loaded silk films improved stability compared to storage in solution or as dry powder Stabilization persisted above physiological temperatures (e.g. up to 60°C) at least 6 months Bioactivity of erythromycin sustained over a month in hydrated sponge	Pritchard et al., in preparation
Tetracycline	Bulk loaded silk films (silk and antibiotic solutions mixed, cast on microneedle array PDMS molds, dried; films rendered insoluble by water annealing or methanol)	Bioactivity of incorporated tetracycline confirmed based on growth inhibition of S. aureus lawns	Tsioris et al., 2011
Doxorubicin	Bulk loaded silk films (silk and antibiotic solutions mixed, cast on microprism array (MPA) PDMS molds, dried; films rendered insoluble by water annealing)	After 3 weeks stored at -20°C (frozen) and 60°C, fluorescence of the doxorubicin stored in silk films did not significantly decrease, compared to less than 80% and 30% of fluorescent doxorubicin remaining when stored in solution at -20°C and 60°C, respectively	Tao et al., submitted
Phenol-sulfon-phthlein (Phenol Red)	Bulk loaded silk films (silk and HRP solutions mixed, cast on nanopatterned PDMS molds, dried; films rendered insoluble by water annealing)	Functionality (i.e. pH sensing capability) of incorporated indicator demonstrated by immersing Phenol Red-loaded films in solutions of varying acidity and observing resulting spectrum variations	Lawrence et al., 2008
4-amino-benzoic acid	Chemically coupled to silk film	Functionality (i.e. pH sensing capability) and stability of the silk-coupled indicator demonstrated over a wide pH range	Tsioris et al., 2010