In Vitro and In Vivo Profiles and Characterization of Insulin Nanocarriers Based in Flexible Liposomes Designed for Oral Administration

Author(s): Sara Melisa Arciniegas Ruiz , María Josefa Bernad Bernad , Raquel Lopez Arellano , Roberto Diaz Torres , Sara Del Carmen Caballero Chacón , Dinorah Vargas Estrada* .

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 8 , 2019

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Graphical Abstract:


Background: Alternatives routes of delivery for Insulin have been evaluated to improve treatment for Diabetes Mellitus. The oral route is the most convenient physiologically; it releases in a similar way to endogenous secretion. Flexible liposomes have deformable abilities to pass through membranes with adequate therapeutic effects, but they have been tested only dermally.

Objective: Our aim was to develop an oral nanocarrier based on flexible liposomes for insulin with polymer addition to reduce gastrointestinal degradation.

Methods: Different percentages of polyethylene glycol were added to a conventional formulation of flexible liposomes. The manufacturing procedure was the heating method. Z potential, size particle, polydispersity index and encapsulation percentage were evaluated. A release profile was performed in the stomach and intestinal pH mediums by two-stage reverse dialysis method. The in-vivo test was performed in experimental diabetic rats by oral, transdermal and subcutaneous routes.

Results: All the formulations showed polydispersity but adequate Z potential. The 10% PEG formulation obtained the best insulin enclosure with 81.9%. The insulin integrity after preparation was confirmed by polyacrylamide gel electrophoresis. PEG and non-PEG formulations showed similar behavior in acid release profile but the release and stability of lipid structures were better and longer in intestinal pH conditions. In vivo tests showed a reduction to normal glucose levels only in subcutaneous route.

Conclusion: The polymer inclusion in flexible liposomes generates an adequate nanocarrier for proteins in terms of stability and composition; although its in-vivo use reduces glucose levels in subcutaneous route, the effect was not adequate in oral route.

Keywords: liposome, lipid vesicles, insulin, diabetes, PEG formulation, nanocarrier, transfersome, nanoparticle.

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Year: 2019
Page: [948 - 960]
Pages: 13
DOI: 10.2174/1570180816666190110112929

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