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Development Of Glucose-triggered PH-sensitive Liposomes For A Potential Insulin Delivery

Kim Chong-Kook, Im Eun-Bin, Lim Soo-Jeong, Oh Yu-Kyoung, Han Seok-Kyu
Published 1994 · Chemistry

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Abstract pH-sensitive liposomes (pH-SL) have been studied as a glucose-responsive insulin delivery system. pH-SL were prepared using (β-palmitoyl-γ-oleoyl- l -γ-phosphatidylethanolamine and oleic acid. pH-dependent destabilization of the pH-SL was tested by the release of a fluorophore, aminonaphthalene-3,6,8-trisulfonic acid (ANTS) from the liposome coencapsulating a quencher, N , N -p-xylenebispyridinium bromide. At pH above 6.9, the release of liposomal ANTS was less than 5%, but below pH 6.4, it increased linearly with decreasing pH down to pH 5.4. The liposomes were aggregated at acidic pH, but were restored to a fine dispersion at neutral pH. To develop pH-SL as a glucose-triggered insulin delivery system, glucose oxidase (GOD) and insulin were coencapsulated in the liposomes. GOD played the role of a sensor of glucose by converting the permeated glucose to gluconic acid that led to the destabilization of the liposomal membrane releasing the content, insulin. The amount of glucose permeated into the liposome was dependent upon the external glucose concentration. Glucose permeated into the liposomes rapidly and the liposomal glucose concentration reached a maximum within 30 min. At the higher glucose concentration (900 mg/dl), the destabilization of GOD-encapsulated pH-SL was promoted, and the release of insulin was 7–8-fold enhanced compared to the lower glucose concentration (90 mg/dl). These results suggest that pH-SL coencapsulating insulin and GOD might have the potential to be developed as a glucose-triggered insulin delivery system.
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