Table 1 Physicochemical parameters for different types of insulin nanocarrier

Chitosan-insulin

Graft polymerization

Carboxylated chitosan + methyl methacrylate

251 to 319

–22 to –26.4

Oral

85

11.9

15 (min)

100 (max)

9.7

[77]

Polyelectrolyte complexes + oily dispersion system

Chitosan + Oleic acid + Plurol oleique + Labrasol

108

29.97

Oral

30.38 to 78.81

–

50

7

[76]

Iionotropic pre-gelation + polyelectrolyte complexation

Chitosan + Alginate

748

−5.6

Oral

72.8

9.9

25 (min)

100 (max)

7.1 to 3.4

[79]

Polyelectrolyte complexation

Chitosan + Dextran sulfate

527

−20.6

Oral

69.3

2.3

50 (min)

100 (max)

5.6 to 3.4

[78]

Ionotropic gelation

Chitosan + TPP + Poloxamer 188

250 to 400

27.31 to 40.71

Oral

59.6 to 88.6

7.0 to 26.3

7 (min)

21 (max)

14 to 15.3

[60]

Ionotropic gelation

Chitosan + TPP

269 to 688

21.8 to 49.8

Oral

38.5 to 78.5

60.8

50 (min)

100 (max)

–

[64]

Ionotropic gelation

Chitosan + TPP

300 to 400

54 to 25

Pulmonary

87.4 to 96.7

19 to 55

5

–

[68]

Polyelectrolyte complexation

Chitosan

200 to 500

8.8 to 22

–

81.4 to 94.8

90

–

–

[67]

Ionotropic gelation

Chitosan + Poly(ç-glutamic acid)

110 to 150

−23.7 to 33.4

Oral

56.8

14.9

15 (min)

30 (max)

–

[70]

Ionotropic complexation + coacervation

Chitosan + Dextran sulfate + Alginate

423 to 850

–

Oral

3 to 94

5 to 13

–

–

[71]

Coacervation method

Chitosan + Eudragit L100-55 

135 to 199

−20.7 to −27.9 mV

Oral

3.38

30.56

–

–

[72]

W/O/W multiple emulsion + polyelectrolyte cross-linking

Chitosan + Alginate + Calcium chloride + Labrafac CC + Phospholipid + Span 80 + Cremorphor EL

488

−62.25

Oral

47.3

–

25 (min)

50 (max)

8.19 to 7.84

[74]

Polyelectrolyte complexation

Chitosan + γ-PGA

185.1 to 198.4

29.9 to 27.8

Oral

40.1 to 55.1

5.2 to 14.1

30

13.0

[65]

PLGA-Insulin

Reverse micelle–solvent evaporation method

PLGA + Phospholipid + PVA

102 to 428

−12 to −22

Oral

51.5 to 90.4

4

20

7.7

[82]

Emulsion solvent diffusion method 

PLGA + Hp55 

169

–

Oral

65.41

3.17

20

6.27

[47]

W/O/W solvent evaporation technique

PLGA + Chitosan + Pluronic 188

134.4

43.1

Oral

52.76

1.29

15

10.5

[87]

W/O/W solvent evaporation technique

PLGA + Pluronic 188

121.3

−1.72

Oral

46.87

1.14

15

7.6

[87]

Hydrophobic ion pairing + emulsion solvent diffusion method

PLGA + Sodium oleate + PVA

161

−33.4

Oral

91.2

–

20

11.5

[88]

W/O/W double emulsion method

Poly(d,l-lactide-co-glycolide) + poly(ethylene glycol)

120 to 355

–

–

95

–

–

–

[89]

W/O/W double emulsion method

β-cyclodextrin-PLGA

120 to 355

–

–

95

–

–

–

[89]

Double-emulsion solvent evaporation method

PLGA + PEG + Folate

∼260

–

Oral

87

∼6.5

50

–

[90]

Dextran-insulin

Emulsion method

Dextrans + Epichlorohydrin + vitamin B(12)

160 to 250

–

Oral

45 to 70

2 to 4

20

11.4 to 26.5

[102]

Ionotrophic gelation + polyelectrolyte complexation

Dextran + Alginate + Poloxamer + Chitosan + BSA

396

−38.2

Oral

–

–

50

13

[103]

Nanoemulsion dispersion + triggered instantaneous particle gelation

Dextran + Alginate + Chitosan + PEG + BSA

>1842 (90 %)

>812 (50 %)

−7

Oral

85

–

25 (min)

100 (max)

42 to 10

[104]

Polyalkylcyanoacrylate-insulin

Microemulsion

Isopropyl myristate + Labrasol + Plurol Oleique + Ethyl (2) cyanoacrylate

200 to 400

−22 to −11.4

Oral

16 to 32.6

1.82 to 0.62

100

–

[109]

Microemulsion

Isopropyl myristate + Labrasol + Plurol Oleique + butyl (2) cyanoacrylate

200 to 400

−21.5 to −6.5

Oral

11.5 to 52.3

1.31 to 0.99

100

–

[109]

–

Polybutylcyanoacrylate + Tween 20

78

–

Oral

–

–

50

15.5

[110]

–

Polybutylcyanoacrylate + Tween 20 + Soyabean oil + vitamin E

67

–

Oral

–

–

50

22.4

[110]

Solid lipid-insulin

W/O/W double emulsion technique

Cetyl palmitate

361

−3.4

Oral

43

–

50

5

[115]

–

Lecithin + stearic acid + ploxamer + wheat germ agglutinin-N-glutamyl-phosphatidyl-ethanolamine

75.3

−13.11

Oral

17.89 to 23.72

–

50

6.08

[117]

Reverse micelle-double emulsion 

Sodium cholate (SC) + soybean phosphatidylcholine + stearic acid + palmitic acid 

114.7

−51.36

–

97.78

18.92

–

–

[118]

W/O/W emulsion technique

–

2 µ

–

Pulmonary

56.32 to 66.02

–

8

35.62

[124]

Double emulsion method

Stearic acid/octadecyl alcohol/cetyl palmitate/glyceryl monostearate/glyceryl palmitostearate/glyceryl tripalmitate/glyceryl behenate

213 to 444.8

−9

Oral

–

–

50

2.92 to 4.53

[123]

Solvent emulsification-evaporation

Witepsol 85E

243

−25

Oral

43.6

2.1

25

8.26

[122]

Solvent emulsification-evaporation

Witepsol 85E + chitosan

470

34

Oral

52.2

1.4

25

17.7

[122]

Targeted insulin nanoparticle

Ionotropic gelation method

N-trimethyl chitosan chloride + CSKSSDYQC peptide + 

342

3

Oral

55.4

–

50

5.66

[26]

Nanoprecipitation

PLA-PEG + human polyclonal IgG Fc

63

−5.6

Oral

–

0.5

1.1

13.7

[128]