Table 4.

Solid silk formats for controlled delivery of therapeutics

Silk source	Formulation	Outcome / Benefits	Released Agents	Ref.
B. mori, Fibroin	Disk	Local delivery of HIV inhibitors (rectal & vaginal) Sustained release for over 4 weeks Higher microbicide stabilization during storage (up to 14 months)	HIV inhibitors: Griffithsin Griffithsin-C37 5P12-RANTES 5P12-RANTES-C37	124
		Sustained released up to 31 days for both IgG and 5P12-RANTES Preserved stability of antibody HIV inhibition in both blood and human colorectal tissue	IgG 5P12-RANTES	125
	Fiber mat	Silk – gelatin fiber mats Controlled release for 36h	Methylene Blue	126
		Controlled delivery (up to 3 months) Local delivery of human platelet lysate for wound healing Improved storage and handling of human platelet lysate	Human platelet lysate FITC-albumin	127
		Silk membrane attached on anal fistula plug For Crohn’s disease treatment Controlled dual drug release (up to 10 days)	Curcumin 5-aminosalicylic acid	62
		Silk electrospun nanofibers combined with silk nanoparticles Dual drug delivery Sustained release for 40 hours	Doxorubicin HCl Curcumin	128
	Film	Sustained release (up to 28 days) Higher efficacy with intratumoral application of films when compared to intravenous application of drugs	Doxorubicin Crizotinib	122
		Sustained release (up to 14 days)	Vincristine, Doxorubicin	120
		Sustained release of cytokines for macrophage polarization Release up to 10 days	IFN-γ. IL-4	119
		Transdermal delivery Chitosan-silk fibroin cross-linked films pH dependent release (pH2>pH 5.5> pH 7.2) over 10h Released drug: salicylic acid>theophylline>diclofenac sodium>amoxicillin	Theophyllin Diclofenac Sodium Amoxicillin Salicylic acid	114
		Silk/gelatin blend film for wound healing In vitro release up to 48 hours In vivo rat model → faster healing in 7 days PEG-modified film allowed better uptake results	Ciproflaxin	132
		Stabilization of antibiotics Implant systems for focal delivery of antibiotics Sustained release (up to 5 days from the films)	Penicillin Ampicillin Gentamicin Cafazolin Rifampicin Eryhtromycin Tetracycline	109
		Designed to be used as a nerve conduit in peripheral nerve defect NGF release for over 3 weeks PC12 cells proliferation and maturation	Nerve growth factor	133
		Heparin releasing composite material against thrombosis Silk fibroin and polyurethane films Controlled release up to 24 hours	Heparin	115
		Controlled release for 29 hours Diffusion model for in vitro release	FITC-dextran	117
		Controlled delivery up to 30 days Effects of silk degumming time on drug release was investigated	Azoalbumin Reactive-red 120, Rifampicin Indigo carmine	118
		Alginate/silk fibroin blend films Controlled release for over 30h Higher release rate with higher alginate ratio	Tetracycline	116
		Controlled release up to 30 days Intratumoral application → slower tumor growth	Doxorubicin	121
		Sustained release without a burst with silk/gelatin/glycerin films Release up to 350 minutes using films Release up to 24h using spray-dried microparticles	Naproxen	134
	Coating	Sustained release up to 40 days with layer by layer silk coating	Rhodamine B Evans Blue Azoalbumin	135
		Multi layer silk coating for vascular stent Reduced platelet adhesion Promotion of human aortic endothelial cell proliferation	Heparin Paclitaxel Clopidogrel	136
		Layer by layer heparin-silk nanofilms Controlled release up to 7 days Higher efficacy against cancer cells with higher beta sheet ratio	Epirubicin Hydrochloride	137
		Silk used as the film coating material on a tablet 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC) and Polyethylene glycol (PEG) blends Sustained release following zero order kinetics Enhanced release with EDC blend	Theophyllin	113
	Foams	Intratumoral implantation → decreased tumor growth Sustained release up to 48 days release	Vincristine	123
		Sustained release Dual combination of vincristine and doxorubicin Intratumoral injections→ significant decrease in tumor growth Reduced systemic exposure	Vincristine Doxorubicin	19
	Microneedles	Controlled release up to 48h Mild drug encapsulation method 10-fold reduction in bacterial density	Horseradish peroxidase (HRP) Tetracycline	93
		Swellable silk fibroin microneedles for trandermal delivery Better release kinetics over non-swellable microneedles Release up to 95 hours/ high mechanical strength	FITC-dextran	129
		Microneedles using polydimethylsiloxane (PDMS) mold PEG diacrylate and sucrose as needle matrix Release kinetics controlled by sucrose content Up to 144h release	Rhodamine Indocyanine green Doxorubicin	138
		Vaccine coated on silk microneedles Transdermal application on mice (24hours) Booster immunization 2 weeks after initial dose In vivo immune response >28 days	Vaccination against: Influenza C. difficile Shigella	130
	Reservoirs	Silk rod reservoirs – implant systems for cancer therapy Sustained release up to 91 days following zero order kinetics	Anastrozole	22
		Sustained release up to 14 days following zero order kinetics Implant system for local delivery of adenosine for epilepsy	Adenosine	139
		Sustained release up to 30 days Entrapment of drug powder allows high drug loading Intratumoral application → decrease in tumor growth	Cisplatin	140
	Wafer	Sustained release up to 45 days Intratumoral application → decrease in tumor growth Tumor cell necrosis adjacent to wafers	Etoposide	20
		Sustained release up to 7 weeks Intratumoral application → decrease in tumor growth Survival up to 60 days	Vincristine	123
Spider Silk eADF4(C16)	Films	Mono- and multi-layer films→ prolonged release (90 days) Release correlated with molecular weight of the drug	Paracetamol FITC-dextran FITC-BSA	141