Table 3.

Silk-based gel systems for controlled delivery of therapeutics

Silk source	Formulation	Outcome/ Benefits	Released Agents	Ref.
B. mori, Fibroin	Lyogels & Hydrogels	Controlled release of IgG1 Longer release with lyogels compared to hydrogels (38 days) Antibody maintained activity	IgG1	104
		Controlled release of IgG1 (26 days) Higher release with hydrated gel (lowest density of silk) Antibody oxidation levels decreased with addition of methionine	IgG1	105
	Gels	Sustained release (25 days) Dual combination of vincristine and doxorubicin Intratumoral injections→ significant decrease in tumor growth Higher intratumoral drug concentration than IV administration Reduced systemic exposure	Vincristine Doxorubicin	19
		Sustained intratumoral delivery via multiple injections (80 days) Diffusion distance halved, growth inflexion time doubled	Vincristine	21
		Intratumoral injections→ significant decrease in tumor growth Slower tumor growth compared to foam format	Vincristine Doxorubicin	106
	Hydrogels	Controlled release (30 days) Mixed with polyacrylamide to yield semi-interpenetrating gels Hydrogel with better mechanical properties Maximum release achieved with 70:30 of silk/polyacrylamide ratio	Trypan blue FITC-inulin	107
		Controlled release and degradation (up to 42 days) In vivo degradation Improved mechanical properties by embedding silk fiber mat in hyaluronic acid network Sufficient mechanical strength for fastening to tissues in vivo	Dexamethasone Hydrocortisone 6a-methylprednisolone Cortisone, Prednisolone Prednisone VEGF, FITC-dextran	108
		Stabilization of antibiotics Focal delivery of antibiotics Sustained release (up to 4 days from the hydrogels) In vivo ampicillin efficacy in a murine infected-wound model	Penicillin Ampicillin Gentamicin Cafazolin Rifampicin Eryhtromycin Tetracycline	109
		Drug release over 8 weeks pH- and concentration-dependent release kinetics Thixotropic hydrogel structure → injectable Significant antitumor response in vivo	Doxorubicin	99
		Doxorubicin release over 4 weeks Intratumoral injection – Reduced tumor growth Minimized systemic side effects	Doxorubicin	61
		Curcumin-loaded cationic nanoparticles in silk fibroin hydrogel Deeper skin penetration in mouse with psoriasis In vitro sustained release for over 72 hours with no burst	Curcumin	110
		Controlled release (28 days) High crystallinity and high drug loading	Risperidone	111
		Sustained ocular delivery - release over 90 days Intravitreal injection – biodegradation starts after 3 months Drug available in vitreous 90 days after injection	Bevacizumab	100
		Extended release over 5 weeks Acid-modified silk hydrogels prevented burst release	Chemokine CXCL12	112
		Acidic fibroin hydrogels (pH 3.8) – polycaprolactone nanofibers Local bone delivery – promoted bone remodeling	Bone morphogenetic protein 2	92
		Silk nanoparticle loaded silk hydrogels – Dual drug delivery	FITC and Rhodamine B	103