Table 2.
Representative materials for construction of oral insulin delivery nanosystems.
| Materials | Carrier Components | Method | Active Components | EE%; LE% | Size (nm); PDI | Zeta-Potential (mV) | In Vitro Release Study (Condition, Time, Insulin Release) | Dose (IU kg−1) | In Vivo Studies | References |
|---|---|---|---|---|---|---|---|---|---|---|
| PLA | PLA, F127 [(PLA-F127-PLA) aggregates)] | Self-assembly | - | -; - |
56; - |
- | pH 7.4, 2 h, 55% | 50 | BGL, 5 h a, 25% b |
[85] |
| PLA, PEG | Nanoprecipitation | IgG Fc | -; 0.5 |
63; - |
−5.6 | pH 7.4, 2 h, 60%, 10 h, 100% |
1.1 | BGL 7 h, 55% |
[86] | |
| PLGA | PLGA (9.5 kDa) PLGA (100 kDa) |
Reverse micelle-solvent evaporation method | SPC | 80~90; - |
200; - |
−17~−12 | pH 1.2, 2 h, 45%; pH 6.8, 6 h, 65% |
20 | rBA, 7.7% | [87] |
| Double emulsion solvent evaporation | SPC, DSPE-PEG (2000) | 92.36; 2.4 |
176; - |
−31.1 | - | 40 | rBA, 12.2% | [88] | ||
| PLGA (50:50 c, 20 kDa) |
Double emulsion method | N-Trimethyl chitosan | 47.0; 7.8 |
247; - |
45.2 | SGF, 6 h, 54.6%; SIF, 6 h, 72.5% |
20 | rPA, 11.8% | [89] | |
| PLGA (50:50, 8 kDa) |
Double emulsion method | TDCS, Tat (YGRKKRRQRRR) | 58.95; 1.38 |
157; 0.220 |
41.8 | pH 1.2, 6 h, 20%; pH 7.4, 48 h, 15% |
10 | BGL, 12 h, 40%; BGL, 36 h, 80% |
[90] | |
| PLGA polymer (50:50; 20 kDa) | Double emulsion method | Folic acid, Chitosan | 41; 6.83 |
252; 0.237 |
5.99 | pH 1.2, 6 h, 32.2%; pH 7.4, 6 h, 34.9% |
70 | rBA, 7.77% | [91] | |
| MOFs | Fe-based mesoporous MOF | Physical absorption | SDS | 51.6; 35.0 |
100; - |
−18.3 | pH 7.4, 14 h, 50%; pH 6.8, 14 h, 20%; pH 5.4, 14 h, 0 |
50 | rPA, 7.8% |
[92] |
| Zr6-based MOF | Physical absorption | - | -; 40 |
- | - | pH 1.29, 1 h, 10%; pH 7.4, 1 h, 91% |
- | - | [93] | |
| Chitosan | Chitosan, γ-PGA | electrostatic interaction | - | 75; 15 |
250; - |
25 | pH < 7, 100% pH > 7.0, disintegrating |
30 | rBA, 15% |
[94] |
| Chitosan (100 kDa, 90%) | self-assembly method | Hyaluronic acids (200 kDa), Biotin | 71.72; - |
277; 0.06 |
−27.90 | 250 U/mL trypsin, 2 h, 30% | 50 | rBA, 4.6% | [95] | |
| Chitosan (365 and 222 kDa, 86% d), alginate | Electrostatic interaction and Chemical cross-linking | - | 78.3; - |
104; - |
3.89 | pH 1.2, 2 h, 25%; pH 6.8, 2~14 h, 60%~70%; pH 7.4, 14~24 h, 80~85% |
100 | rBA, 8.11% | [96] | |
| Chitosan (200–300 kDa, 85%), snail mucin | Self-gelation method | - | 92.5; 21.4 |
504; 0.185 |
31.2 | pH 1.2, 2 h, 10%; pH 7.4, 10 h, 87% |
50 | rBA, 10.6% | [97] | |
| Chitosan (150 kDa, 85.8%) | Self-assembly method | SDS, L-Phenylalanine | 93.4; - |
131; 0.227 |
30.71 | pH 1.2, 2 h, 45%; pH 6.8, 4 h, 82% |
50 | rPA, 5.8% |
[51] | |
| Chitosan (29.80 kDa, 80.2%) | Chemical cross-linking | Pentaerythritol tetrakis (3-mercaptopropionate) | 79.63; 19.82 |
220; 0.091 |
2.3 | pH 2, 12 h, 96%; pH 5.3, 24 h, 92% |
50 | 3 h, 50% | [98] | |
| Carboxymethyl chitosan | Ionic cross-linking method | L-valine, PBA | 67; 9.8 |
190; - |
- | SGF, 24 h, 16.6%; SIF, 24 h, 50.7%; pH 7.4, 24 h, 55.4%; pH 7.4 (10 mM), 24 h, 68%; pH 7.4 (20 mM), 24 h, 92% |
75 | rPA, 7.55% | [99] | |
| Others | Alginate, dextran sulfate | Emulsification/internal gelation, polyelectrolyte complexation | low molecular weight chitosan, bovine serum albumin | 30.7; 6.2 |
300; - |
28.9 | pH 1.2, 2 h, 35%; pH 5.5, 2–4 h, 100%; pH 7.4, 2~8 h, 100% |
- | - | [100] |
| Proanthocyanidins, short-chain glucans | Recrystallization | - | 70.2; 3.5 |
100~200; - | - | pH 1.2, 8 h, 60%; pH 6.8, 8 h, 75% |
100 | rPA, 6.98% | [101] | |
| HPMCP | Spontaneous emulsification solvent diffusion method | 90.8; 8.13 |
200; <0.27 |
−15~0 | pH 3.0, 4 h, 8.2%; pH 6.0, 4 h, 39.7%; pH 6.8, 4 h, 77.4%; pH 7.4, 4 h, 82.0% |
25 | rBA, 8.6% | [102] | ||
| Waxy corn starch (approximately 99% amylopectin), Chitosan (140 kDa, 90%), |
Self-assembly | - | 89.6; 6.8 |
311; 0.227 | −43.7 | pH 7.4, 8 h, 50% | 50 | rBA, 15.19% | [103] | |
| Silica | - | SiO2 | 20~100; - |
10 | rBA, 23.4% | [39] |
a: The time from medication to glucose level testing; b: hypoglycemic effect; c: degree of deacetylation; d: the ratio of poly (lactic acid) and poly (glycolic acid); PDI: poly dispersion index; EE%: encapsulation efficiency; LE%: drug loading efficiency; rBA: relatively bioavailability, rPA: relatively pharmacological activity; BGL: blood glucose level; SPC: soybean phosphatidylcholine; PBA: phenylboronic acid; DSPE-PEG(2000): 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N-methoxy (polyethyleneglycol)-2000; SDS: sodium dodecyl sulfate; TDCS: N-trimethyl-N-dodecyl chitosan; γ-PGA: poly (γ-glutamic acid); HPMCP: hydroxypropyl methylcellulose phthalate; -: not given in the literature.