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]

Table 1: Oral insulin nano-carriers and experimental results relating to each.