Table 2.

Silk-based nanoparticle and microparticle systems for controlled delivery of therapeutics

Silk source	Formulation	Outcome/ Benefits	Released Agent	Ref.
B. mori, Fibroin	Microparticles	Sustained release over several weeks Increase in in vivo joint residence time	Cy-7	73
		Extended release (up to 25 days) No burst release with methanol treatment Longer release with methanol treatment than NaCl treatment Enzyme activity retained during preparation	HRP	76
	Microparticle coating	Delayed degradation of PLGA microparticles (up to 30 days) Sustained protein release as diffusion barrier	HRP, Rh-BSA	77
	Nanoparticles	Preparation by super critical CO2 – no organic solvent Sustained release (2 days)	Indomethacin	64
		Stimulus responsive pH-dependent release, pH 4.5>>pH 6.0>pH 7.4 (up to 6 days) Enhanced endocytic uptake and lysosomal accumulation	Doxorubicin	24
		Silk- albumin conjugates Sustained release: 85% release over 12 days High drug encapsulation and loading efficiency Cytocompatible	Methotrexate	65
		Sustained release (up to 3 days) Increased curcumin bioavailability Cytotoxic to carcinogenic cells Not toxic to healthy cells	Curcumin	68
		Dual drug loading Drug release for 7 days Suppression of cancer cell growth	Paclitaxel, Doxorubicin	70
		Simple nanoparticle manufacturing Sustained release	Doxorubicin	78
		Silk fibroin (shell) and polyvinyl alcohol (PVA, core) Controlled release for 72h Control of drug release achieved by alternating PVA/silk ratios and by applying ultrasound	Doxorubicin	79
		Drug release over 15 days Internalization in cancer cells Low toxicity in mouse fibroblasts	Cisplatin	66
		Carrier-in-carrier delivery system Silk/curcumin nanoparticles loaded in extracellular vesicles Release of drug for up to 100h Improved curcumin bioavailability	Curcumin	80
		Improved cyto- and hemo compatibility of the drugs High encapsulation efficiency Sustained release up to 56 hours	Celecoxib, Curcumin	81
		Enhanced cellular uptake and prolonged retention time In vitro drug release up to 200 hours In vivo biocompatibility Accumulation and extended retention time in retina following intravitreal injection	FITC-BSA	82
		In vivo transdermal delivery of fluorescent dyes	Rhodamine B (fluorescent dye)	83
	Particles	Release based on charge interactions Prolonged release with positively charged molecules (up to 14 days)	Alcian blue, rhodamine B, crystal violet	84
		High encapsulation efficiency Release up to 7 weeks Bioactivity preserved during \ release	Salicylic acid, propranolol hydrochloride, IGF-I	85
		Targeted and pH-responsive, folic acid-modified particles Controlled release over 32 days Higher drug release at low pH with enhanced cell internalization	Doxorubicin	71
B. mori and A. mylitta Fibroin	Nanoparticles	Accumulation of nanoparticles in cytoplasm of carcinoma cells Sustained release up to 3 weeks	VEGF	86
B .mori PEGylated silk	Nanoparticles	Stealth design for increased clearance time High encapsulation efficiency (>93%) pH-dependent release over 14 days Cytotoxic to breast cancer cells	Doxorubicin	67
	Nanoparticles Microparticles	2 days release, longer plasma exposure Improved curcumin bioavailability Reduced burst release	Curcumin	69
B .mori Sericin	Nanoparticles	2 days release No toxicity from nanoparticle carrier Lower doxorubicin systemic toxicity Stable nanoparticles	Doxorubicin	87
A. mylitta Fibroin	Nanoparticles	Folate-conjugated nanoparticles allow targeted delivery Sustained release up to 21 days with enhanced release at acidic pH	Doxorubicin	88
A. pernyi Fibroin	Nanoparticles	Sustained release up to 23 days pH-dependent release	Doxorubicin	89
	Nanoparticles	Self-assembled nanoparticles using cations (Na+, Ca2+, Ce3+) Sustained/pH-dependent release up to 11 days	Doxorubicin	90
A. pernyi Sericin	Microspheres	Microspheres are made of silk sericin and hydroxyapatite Sustained/pH dependent release of the drug up to 120 hours	Doxorubicin	91
Spider silk N. clavipes	Nanoparticles	Her2 targeted Enhanced targeted binding pH dependent drug release (up to 15 days) Non toxic nanoparticle carriers Higher cytotoxicity for doxorubicin-loaded nanoparticles	Doxorubicin	72