Table 1.

Examples of NPs-based insulin delivery systems.

Nano-carrier	Size; Zeta potential	Entrapment efficiency (%)	Drug loading	Dose	Efficacy	Ref.
Insulin-coated gold NPs	20−70 nm; –	–	–	s.c.: 6 mg/mouse	Effect lasting for 6 h	38
Poly(ethylene glycol) capped poly(lactic-co-glycolic) acid NPs	140−170 nm; −14.5 mV	66	–	s.c.: 2 IU/kg	Effect lasting for ∼6 h	42
Poly(ethylene glycol) (PEG) and polylactic acid (PLA)-based copolymeric NPs	181.9 nm; –	58.5	313.4 IU/g	s.c.: 25, 50 IU/kg	Effect lasting for more than 7 days	43
Insulin phospholipid complex-loaded biodegradable PHBHHx NPs	182.4 nm; −36.93 mV	87.19	–	s.c.: 4 IU/kg	Pharmacological availability (PA) 350.29%; effect lasting for ∼83.5 h	44
NPs loading insulin and glucose enzymes coated by chitosan or alginate	340 nm/293 nm; 10.6 mV/−11.5 mV	54.1/77.9	7.9%/11.4%	s.c.:−	Effect lasting for 10 days without peaks of hyperglycemia or hypoglycemia	52
Enzyme (GOx and CAT) nanocapsules loaded in chitosan microgels	12 nm; –	59.7	44.6%	s.c.: 40 mg/kg	Effect lasting for 24 h	62
Microparticles composed of chitosan, Con A and dextran	2.5 μm; –	92.2	9.1%	–	In vitro: glucose responsive insulin release	74
Poly(ethylene glycol)-b-Poly(acrylic acid-co-acrylamidophenylboronic acid) (PEG-b-(PAA-co-PAAPBA)) micelles	130 nm; –	–	29%	–	In vitro: glucose responsive insulin release	85
p(3-acrylamidophenylboronic acid-b-diethylene glycol methyl ether methacrylate) NPs	Submicron−sized; ‒37.2 mV	∼70	∼15%	s.c.: 0.4 mg/kg	In vitro: glucose- and temperature-sensitive insulin release In vivo: effect lasting for 48 h	86
Cetyl palmitate-based solid lipid NPs	361 nm; ‒3.4 mV	43	–	p.o.: 50 IU/kg s.c.: 2.5 IU/kg	PA 1.6%; effect lasting for 24 h	99
INS-loaded polymer–lipid hybrid NPs	176 nm; ‒31.1 mV	92.30	2.40%	p.o.: 40 IU/kg s.c.: 5 IU/kg	RBA 12.42%; effect lasted for 24 h	104
Insulin/L-penetratin complex NPs coated with hyaluronic acid	103.7 nm; ‒19.7 mV	97	67%	p.o.: 80 IU/kg s.c.: 5 IU/kg	BAR 11%; PA 3.7%; blood glucose level (BGL) reduced by 60% in 8 h	106
CS/γPGA-DTPA NPs (CS: chitosan; γPGA: poly(γ-glutamic acid); DTPA: diethylene triamine pentaacetic acid)	246.6 nm; +37 mV	75.70	16.30%	p.o.: 30 IU/kg s.c.: 5 IU/kg	BAR 19.7%; prolonged reduction in BGL	107
Polyester poly(-ε-caprolactone) and a polycationic non-biodegradable acrylic NPs	358 nm; +41.8 mV	96	–	p.o.: 50 IU/kg (PK); 100IU/kg (PD)s.c.: 10 IU/kg	BAR 13.21%; reducing the glythemia–time curve area by 38%	109
TMC-based NPs coated with pHPMA (TMC: trimethyl chitosan; pHPMA: N-(2-hydroxypropyl) methacrylamide copolymer)	163 nm; ‒3.35 mV	54.10	24.50%	p.o.: 50 IU/kg s.c.: 5 IU/kg	BAR 8.56%; maximal BGL reduced 36% at 4 h; effect lasting for 10 h	114
Cell-penetrating peptide (CPP) grafted chitosan NPs	316 nm; +42 mV	–	–	p.o.: 30 IU/kg s.c.: 5 IU/kg	BAR 19.6%; BGL reduced 30% in 4 h and the effect lasted for 12 h	115
Lectin-modified solid lipid NPs	75.3 nm; ‒13.1 mV	40.18	–	p.o.: 50 IU/kg s.c.: 2 IU/kg	BAR 7.11%; PA 6.08%	121
Vitamin B12‒nanosphere conjugate	160–250 nm; –	45–70	2%–4%	p.o.: 20 IU/kg s.c.: 0.4 IU/kg	PA 11.4–26.5%; effect prolonged for many hours	123
Vitamin B12 coated dextran NPs	192 nm; –	63.50	3%	p.o.: 20 IU/kg s.c.: 0.4 IU/kg	PA 29.4%; BGL reduced 70%–75% and effect lasting for 54 h	124
PEGylation and Con A-based targeted NPs	196.3 nm; ‒25.6 mV	44.60	–	p.o.: 20 IU/kg s.c.: 0.4 IU/kg	A delayed (2–4 h) reduction of BGL and effect lasting for 24 h	125
FA-PEG-PLGA NPs	260 nm; –	87	6.50%	p.o.: 50 IU/kg s.c.: 5 IU/kg	BAR 19.62%; PA 20.40%; effect lasting for 24 h	126
FA-CS NPs	288 nm; +21.90 mV	>80	–	p.o.: 50 IU/kg s.c.: 5 IU/kg	BAR: 17.04%; significant decrease in BGL in 6 h and down to baseline at 24 h	127
Cp1-11 peptide/insulin-loaded NPs	237.2 nm;–	90.43	28.06%	p.o.: 50 IU/kg s.c.: 4 IU/kg	PA 9.83%; BAR 15.62%; BGL reduced to 55.1% in 2 h and maintained 60% for 8 h	128
Zein-carboxymethylated short-chain amylase/CS nanocomposites	311.32 nm; 43.77 mV	89.60	6.80%	p.o.: 50 IU/kg s.c.: 5 IU/kg	PA 14.12%; BAR 15.19%; effects lasting for up to 8 h	129

‒Not applicable.