NP formulation |
Experimental model |
Observation |
Reference |
CS |
CS NPs |
Diabetic rats;
Caco-2 cell monolayer |
Prolonged hypoglycemia;
TJ opening effect |
[6,58]
[6,10,59-61] |
CS-γPGA NPs |
Diabetic rats |
Prolonged hypoglycemia;
BA 15% (20% when the NPs were enteric-coated) |
[6,10,60,62,63] |
CS/γPGA-DTPA NPs |
Diabetic rats |
Prolonged hypoglycemia;
BA 20% |
[64] |
CS derivatives |
TMC/γPGA NPs |
Caco-2 cell monolayer |
TJ opening effect |
[6,65] |
TMC-CSK NPs |
Caco-2/HT29-MTX co-culture;
Diabetic rats |
Enhanced absorption via clathrin- and caveolae-mediated endocytosis;
Greater hypoglycemic effect;
Increase BA by 1.5-fold (compared to unmodified TMC NPs) |
[66] |
TMC-Cys NPs |
Caco-2 cell monolayer;
Rat intestinal model |
Improved absorption |
[6,67,68] |
HTCC NPs |
In vitro |
TJ opening effect |
[69] |
PLGA |
PLGA NPs loaded with insulin-PL complex |
Diabetic rats |
BA 7.7%
|
[6,70] |
PLGA-HP55 NPs |
Diabetic rats |
BA 6.27% |
[6,71,72] |
PLGA/RS NPs (in HP55-coated capsules) |
Diabetic rats |
Prolonged hypoglycemia;
Pharmacological availability ~9.2% |
[73] |
Antacid-incorporated PLGA NPs |
Diabetic rats |
Oral bioavailability 6 times higher than native insulin |
[74] |
CS-PLGA NPs |
Diabetic rats |
Greater bioadhesion;
PA 10.5% |
[75] |
Acrylic-based |
PAA-Cys NPs |
Diabetic rats |
Increase in mucoadhesivity;
2.3-fold increase in area under the curve of insulin |
[6,76] |
PIBCA NPs |
Diabetic rats |
Significant increase in absorption;
Prolonged hypoglycemia |
[77] |
PACA NPs |
Diabetic rats |
Prolonged hypoglycemia (36 h) |
[78] |
P(MAA-g-PEG) and P(AA-g-PEG) NPs |
Diabetic rats |
Protected insulin at low pH;
Prolonged hypoglycemic (>6 h);
Up to 50% glucose reduction |
[79] |
poly(PEGDMA:MAA) microparticles |
Diabetic rats |
pH-sensitive;
Prolonged hypoglycemia (8-10 h) |
[80] |
PLA |
PLA-F127-PLA NPs |
Diabetic mice |
Prolonged hypoglycemia (23 h) |
[6,81] |
PCL |
PCL/RS NPs |
Diabetic rats |
52% blood glucose reduction |
[6,82,83] |
Poly(allylamine) |
Insulin-poly(allylamine)
NPs |
Caco-2 cell monolayer;
In vitro |
Reduced pepsin, trypsin and chymotrypsin degradation;
Improved transcellular and paracellular transport;
TJ opening effect |
[6,84-86] |
Dextran |
VB12-dextran NPs
|
Diabetic rats |
Prolonged hypoglycemia (54 h);
70-75% blood glucose reduction;
PA 29.4% |
[6,45-47] |
Liposomes |
DPPC/cholesterol |
Normal & diabetic rats |
Greater hypoglycemic effect;
Protection against degradation in the GI tract and entered the bloodstream intact |
[87] |
WGA-, TL- and UEA1-modified liposomes |
Normal rats& diabetic mice |
Hypoglycemic effect;
BA 9.12% (WGA), 7.89% (TL) and 5.37% (UEA1) |
[88] |
NaTC liposomes |
Normal mice |
Greater hypoglycemic effect |
[89] |
SLNs |
Cetyl palmitate-based SLNs |
Diabetic rats |
Prolonged hypoglycemia (24 h);
PA 5.1% |
[6,90] |
(WGA-N-glut-PE)-modified SLNs |
In vitro;
Normal rats |
Greater protection against enzymatic degradation;
PA 6.08% |
[51] |
