Enzyme triggered pH sensitive liposomes for insulin delivery

In spite of encouraging results of alternative parenteral dosage forms, the problems of type I diabetes and insulin delivery remain a challenging area of research. Glucose responsive liposomes (GR) containing encapsulated insulin and GOD were prepared using defined molar ratios of DPPE, Egg PC, cholesterol and any of three different fatty acids viz. oleic acid (GR-O1& GR-O2), palmitic acid (GR-P1& GR-P2), stearic acid (GR-S1& GR-S2). The control formulations include a non-glucose responsive liposome (PS-L; no GOD) and non-pH-sensitive liposome (NP-L; no pH-sensitive component). The GR formulations showed a marked aggregation at pH 6.8-6.4 and a glucose concentration dependent permeation and destabilization. In vitro, insulin release was 21-31% within 0.5 h at 100 mg/dL glucose incubation and was doubled (52-62%) at 250 mg/dL; the release was slightly higher with the formulations of 2 molar ratios of fatty acids. Following s.c. injection, the GR formulation showed higher responses to reduce blood glucose (percentage of initial is expressed) and were found to be 40-50% compared to control formulations (PS-L; 61% and NP-L; 67 ± 5.5%). Nonetheless, tailoring of controlled release and long circulating forms of this carrier system may improve its potential.