Table 2.
Studies on nasal insulin formulations.
| Polymers/Others | Delivery system | Enhancer | Animal model | Results | Ref. |
|---|---|---|---|---|---|
| Degradable starch | Microspheres | LFC | Sheep | While the relative bioavailability of insulin from microspheres was 10.7%, addition of enhancer to the formulation, bioavailability of insulin was increased to 31.5%. | [45] |
| Soluble starch | Powder and Microspheres | - | Rats | A comparison between microspheres and starch powders (mw 11000 and 25000) indicated that the insoluble starch of mw 25000 and the microspheres reduced the plasma glucose level to the same extent. Besides water soluble starch powder (mw 11000) did not change the plasma glucose level. | [46] |
| Crosslinked starch and Dextran | Microspheres | Epichlorohydrin | Rats | The effect on the glucose level of insulin from starch and dextran microspheres was rapid and maximum decrease in plasma glucose level was achieved in 30-40 minutes. The effect of starch microspheres was found more efficient than that of dextran microspheres to decrease blood glucose level. | [47] |
| Starch- Carbopol® 974P and maltodextrin -Carbopol® 974P | Freeze-dried powder | - | Rabbits | The nasal bioavailability achieved with the application of Starch-Carbopol® 974P powder was significantly higher than that of the maltodextrin-Carbopol® 974P mixtures. | [48] |
| Starch | Microspheres | Bile salt derivatives (LFC, GDC, STDF) | Sheep | Bioadhesive starch microspheres have improved transport of insulin across nasal membrane in the presence of absorption enhancers. Addition of enhancer to the microspheres has increased insulin absorption than that of absorption enhancer in solution. | [49] |
| Amioca® starch and Carbopol® 974P | Powder | - | Rabbits | Following nasal single-dose application of a physical mixture of Amioca® starch and Carbopol® 974P (9/1) the bioavailability of insulin has been found to be more than 10%. | [50] |
| Crosslinked starch | Nanoparticles | SGC, LFC | Rats | A rapid hypoglycemic effect has been observed with nasal application of nanoparticles. It has been emphasized that the release of insulin from nanoparticles can be modified by adjusting the degree of cross-linking. The release rate of insulin has significantly increased with combination of permeation enhancers and nanoparticles. | [52] |
| Dextran | Microspheres | - | Rats | Microspheres with insulin on the surface were more effective in promoting insulin absorption than those with insulin distributed within the dextran matrix. | [53] |
| Anionic resin (SPS), nonionic resins (PAE, SDBC) and cationic resin (CA) | Powder | - | Rabbits | Nasal administration of insulin mixed with anionic resin caused a rapid increase of the plasma insulin level, while nasal administration of insulin alone caused little increase. Nonionic resin (SDBC) showed similar enhancement in nasal insulin absorption in contrast, the other nonionic resin and cationic resin did not improve insülin absorption. |
[54] |
| Hyaluronic acid ester | Microspheres | - | Sheep | Average relative bioavailability of insulin from microspheres was calculated as 11% when compared with insulin administered by subcutaneous route. | [55] |
| Chitosan | Nanoparticles | - | Rabbits | The freeze-dried formulation of insulin-loaded chitosan nanoparticles has led to a greater decrease in plasma glucose level when compared to the insulin chitosan solution. | [56] |
| Cross linked chitosan | Nanoparticles | - | Rats | Microspheres containing chitosan and ascorbyl palmitate caused a 67% reduction of blood glucose compared to intravenous route and absolute bioavailability of insulin was found as 44%. | [57] |
| Thiolated chitosan | Nanoparticles | - | Rats | Insulin-loaded thiolated chitosan microspheres let to more than 1.5-fold higher bioavailability and more than 7-fold higher pharmacological efficacy than unmodified chitosan microspheres. | [58] |
| Chitosan | Nanoparticles | CM-β-CD | - | The fast release of insulin from chitosan/CM-β-CD nanoparticles was observed (84-97% insulin within 15 min.). | [59] |
| Chitosan | Nanoparticles | - | Rats | Nanoparticles containing insulin have increased the pharmacodynamic activity of the drug. The synthesis of gold nanoparticles prepared by using chitosan has used a new method, and therefore, the surface properties of chitosan were improved for binding of biomolecules. | [60] |
| Chitosan | Nanoparticles | NAC | Rats | Nasal administration of chitosan-NAC nanoparticles increased the insulin absorption compare to unmodified chitosan nanoparticles and control insulin solution. | [61] |
| Chitosan | Nanoparticles | SBE-β-CD and CM-β-CD | Rabbits | The nanoparticles have reversibly increased the transepithel resistance of the cells and increased the membrane permeability in in-vitro cell culture studies. Nasal application of fluorescence-loaded nanoparticles to rats has proved their ability to pass through nasal mucosa. In conclusion, insulin-loaded nanoparticles have decreased the plasma glucose level (more than 35% reduction). | [62] |
| Aminated gelatin | Microspheres | - | Rats | Aminated gelatin microspheres have significantly increased the nasal absorption of insulin when administered in dry formulation but no significant hypoglycemic effect was observed when given as a suspension. | [63] |
LFC = Lysophosphatidylcholine; GDC= Glycodeoxychlote; STDF = Sodium taurodihydroxyfusidate.
SPS = Sodium polystrene sulphonate; PAE = Polyacrylester; SDBC = Styrene-diviniylbenzene copolymer; SGC = Sodium glycocolate.
CA = Cholestramine; CM-β-CD = Carboxymethyl-β-cyclodextrin; NAC = N-acetyl-L-Cysteine; SBE-β-CD = Sulfobutylether-β-cyclodextrin.