Insulin PEGylated

Since the first insulin PEGylation studies of Ehrart and Luisi, several investigations have been carried to improve the physico-chemical and biological properties of this hormone by site-specific or random attachment of one or more PEG chains with different molecular weight and shape. Although the array of events which determines changes in the in-vivo behavior of insulin are often difficult to pinpoint, these studies showed that the biopharmaceutical properties of the hormone are... 

Insulin inhalation - Pfizer/NektarTherapeutics HMR 4006, inhaled PEG-insulin - Nektar, PEGylated insulin - Nektar, Drugs R D 2004. 5 166-170. 

P. G. Schmidt. 2005. PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis./. Control. Release 104 447-460. 

Fig. 8.5 Decrease in blood glucose level in diabetic mice after oral administration of thiolated polyacrylate minitablets comprising PEGylated insulin indicated values are mean SD (n = 10) (Calceti et al. 2004)...

Monoclonal andbody directed insulin or Tf receptors were also udhzed to target PEGylated immunoliposomes for d ansvascular... 

FIGURE 40.14 Plasma glucose levels after subcutaneous administration of pegylated insulin (O), and pegylated insulin/y-CyD polypseudorotaxane in the presence of 116mg/mL (A), or 232mg/mL (A), y-CyD in rats. 

Higashi, T., Hirayama, R, Arima, H., Uekama, K. Polypseudorotaxanes of pegylated insulin with cyclodextrins application to sustained release system. Bioorg. Med. Chem. Lett. 2007,17, 1871-1874. 

As with insulin, longer-acting versions of both EPO and CSE have been engineered, with Aransep being the EPO derivative and Neulasta the pegylated ver-... 

Insulin inhalation—Pfizer/Nektar therapeutic HMR 4006, inhaled PEG-insulin—Nektar, PEGylated insurin—Nektar. Drugs. R.D. 5 166-170. 

FIGURE 40.13 Photographs of precipitates of pegylated insulin/a- and y-CyD polypseudorotaxanes and their interaction modes. 

In a PEC used to deliver a protein, the latter is often used as one of the polyelectrolyte components of the complex. Examples of PECs in which one of the two polyelectrolyte components is an active substance itself, are complexes of chitosan and insulin. The PEC composed of trimethyl chitosan (TMC) and pegylated TMC (PEG-g-TMC) can be obtained simply by mixing the solutions of TMC and insulin at various mass and charge ratios. These PECs were stable in simulated intestinal fluid at pH 6.8. However, they disintegrated in simulated gastrointestinal fluid at pH 1.2. The PECs also protected insulin from temperature-induced denaturation up to 50 °C and from degradation by trypsin. Based on these results, the authors suggested that polyelectrolyte complexation can be a useful technique for fabrication of insulin delivery systems for oral administration. 

PEGylated chitosan nanoparticles were shown to enhance insulin absorption to a greater extent compared with non-nanoparticulate forms of chitosan and insulin alone. Chitosan nanoparticles were also found to enhance nasal absorption of insulin in rabbit, regardless of chitosan molecular weight. Recently, Al-Qadi and co-workers reported that intratracheal administration of diy insulin powder microencapsulated in chitosan nanoparticles increased its distribution to the deep lungs, and facilitated release of a biologically active form of insulin to rat blood. Moreover, they observed a more pronounced and prolonged effect compared to non-formulated insulin. ... 

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