Liposome-encapsulated insulin

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

FIGURE 10.4 Reduction in blood glucose following pulmonary administration of 1 U/kg insulin (a), insulin encapsulated in positively charged liposomes ( ), insulin encapsulated in negatively charged liposomes ( ), insulin encapsulated in neutral liposomes ( ). (Adapted from Li and Mitra 1996). 

H, M. Fate and B. E. Ryman. Oral administration of insulin by encapsulation within liposomes. FEBS Lett. 62 60-63 (1976). 

A prolonged insulin action can also be achieved by encapsulation of insulin in liposomes before subcutaneous injection. The extended hypoglycaemic response is believed to be a result of a lower metabolic clearance rate. Currently, the encapsulation efficiency, however, is only 5% (Spangler, 1990). Further investigations are needed. 

One of the few potential successfiil sustained-release lipid formulations of biomacromolecules is the Depofoam concept by SkyePharma. It is different from the conventional liposomes by the increased surface area available, which makes the aqueous volume larger (122). It has been shown to successfiilly encapsulate (60-85%) and sustain the release of insulin, luteinizing hormone-releasing factor and others (123). 

The liposome gel delivery system and liposome surface modified with fibronectin offer several advantages over other liposome formulations or gel formulations constructed only with free drug [96], Two peptide hormones, insulin and growth hormone encapsulated in vesicles sequestered within the matrix, are slowly released into the circulation from either an intramuscular or subcutaneous injection site. A maximum 3-5-d release for insulin or a 14-d growth hormone release was observed. 

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