Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles

Liat Soudry-Kochavi; Natalya Naraykin; Rosanna Di Paola; Enrico Gugliandolo; Alessio Peritore; Salvatore Cuzzocrea; Ehud Ziv; Taher Nassar; Simon Benita

doi:10.1016/j.ejpb.2018.10.013

Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles

Liat Soudry-Kochavi, Natalya Naraykin, Rosanna Di Paola, Enrico Gugliandolo, Alessio Peritore, Salvatore Cuzzocrea, Ehud Ziv, Taher Nassar, Simon Benita^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system. This drug delivery system (DDS) improved the relative oral bioavailability of exenatide, in comparison to Byetta ^® injection SC. In this study, we report about the efficacy of this DDS to improve glycemic parameters in diabetic ob/ob mice. Our results suggested that our DDS successfully lowered blood glucose levels (BGL) raised insulin levels, decreased glycated hemoglobin and maintained the body weight of the mice. These findings validate the efficacy of this DDS in promoting oral delivery of exenatide and will hopefully improve patient compliance and adherence. The potential of this DDS to encapsulate other leading peptides and proteins, such as insulin, was also evaluated in this study. It was found that peptides up to 6 kDa can be efficiently encapsulated, but the in-vivo performance is also dependent on other physicochemical properties.

Original language	American English
Pages (from-to)	214-223
Number of pages	10
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	133
DOIs	https://doi.org/10.1016/j.ejpb.2018.10.013
State	Published - Dec 2018

Bibliographical note

Funding Information:
We would like to thank Dr. Marina Frusic-Zlotkin and Dr. Yoram Soroka, of The Institute for Drug Research, The Hebrew University of Jerusalem, for their technical assistance. Partly funded by Aurum Ventures ltd, Rama Gan, Israel , via a Yissum Contract No. 0394362 of the Hebrew University of Jerusalem.

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

Diabetes
Exenatide
Microparticles
Nanoparticles
Oral
Peptides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejpb.2018.10.013

Cite this

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title = "Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles",

abstract = " One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system. This drug delivery system (DDS) improved the relative oral bioavailability of exenatide, in comparison to Byetta {\textregistered} injection SC. In this study, we report about the efficacy of this DDS to improve glycemic parameters in diabetic ob/ob mice. Our results suggested that our DDS successfully lowered blood glucose levels (BGL) raised insulin levels, decreased glycated hemoglobin and maintained the body weight of the mice. These findings validate the efficacy of this DDS in promoting oral delivery of exenatide and will hopefully improve patient compliance and adherence. The potential of this DDS to encapsulate other leading peptides and proteins, such as insulin, was also evaluated in this study. It was found that peptides up to 6 kDa can be efficiently encapsulated, but the in-vivo performance is also dependent on other physicochemical properties.",

keywords = "Diabetes, Exenatide, Microparticles, Nanoparticles, Oral, Peptides",

author = "Liat Soudry-Kochavi and Natalya Naraykin and {Di Paola}, Rosanna and Enrico Gugliandolo and Alessio Peritore and Salvatore Cuzzocrea and Ehud Ziv and Taher Nassar and Simon Benita",

note = "Funding Information: We would like to thank Dr. Marina Frusic-Zlotkin and Dr. Yoram Soroka, of The Institute for Drug Research, The Hebrew University of Jerusalem, for their technical assistance. Partly funded by Aurum Ventures ltd, Rama Gan, Israel , via a Yissum Contract No. 0394362 of the Hebrew University of Jerusalem. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

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AU - Soudry-Kochavi, Liat

AU - Naraykin, Natalya

AU - Di Paola, Rosanna

AU - Gugliandolo, Enrico

AU - Peritore, Alessio

AU - Cuzzocrea, Salvatore

AU - Ziv, Ehud

AU - Nassar, Taher

AU - Benita, Simon

N1 - Funding Information: We would like to thank Dr. Marina Frusic-Zlotkin and Dr. Yoram Soroka, of The Institute for Drug Research, The Hebrew University of Jerusalem, for their technical assistance. Partly funded by Aurum Ventures ltd, Rama Gan, Israel , via a Yissum Contract No. 0394362 of the Hebrew University of Jerusalem. Publisher Copyright: © 2018 Elsevier B.V.

PY - 2018/12

Y1 - 2018/12

N2 - One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system. This drug delivery system (DDS) improved the relative oral bioavailability of exenatide, in comparison to Byetta ® injection SC. In this study, we report about the efficacy of this DDS to improve glycemic parameters in diabetic ob/ob mice. Our results suggested that our DDS successfully lowered blood glucose levels (BGL) raised insulin levels, decreased glycated hemoglobin and maintained the body weight of the mice. These findings validate the efficacy of this DDS in promoting oral delivery of exenatide and will hopefully improve patient compliance and adherence. The potential of this DDS to encapsulate other leading peptides and proteins, such as insulin, was also evaluated in this study. It was found that peptides up to 6 kDa can be efficiently encapsulated, but the in-vivo performance is also dependent on other physicochemical properties.

AB - One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system. This drug delivery system (DDS) improved the relative oral bioavailability of exenatide, in comparison to Byetta ® injection SC. In this study, we report about the efficacy of this DDS to improve glycemic parameters in diabetic ob/ob mice. Our results suggested that our DDS successfully lowered blood glucose levels (BGL) raised insulin levels, decreased glycated hemoglobin and maintained the body weight of the mice. These findings validate the efficacy of this DDS in promoting oral delivery of exenatide and will hopefully improve patient compliance and adherence. The potential of this DDS to encapsulate other leading peptides and proteins, such as insulin, was also evaluated in this study. It was found that peptides up to 6 kDa can be efficiently encapsulated, but the in-vivo performance is also dependent on other physicochemical properties.

KW - Diabetes

KW - Exenatide

KW - Microparticles

KW - Nanoparticles

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KW - Peptides

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U2 - 10.1016/j.ejpb.2018.10.013

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M3 - Article

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SN - 0939-6411

VL - 133

SP - 214

EP - 223

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

ER -

Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles

Abstract

Bibliographical note

Keywords

UN SDGs

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