Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Yusuf haggag, Yasser Abdel-Wahab, Opeolu Ojo, Mohamed Osman, Sanna El-Gazawy, Mohamed El-Tanani, Ahmed Faheem, Paul McCarron

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.
LanguageEnglish
JournalInternational Journal of Pharmaceutics
Volume499
Early online date30 Dec 2015
DOIs
Publication statusE-pub ahead of print - 30 Dec 2015

Fingerprint

Nanoparticles
Insulin
Insulin Resistance
Streptozocin
poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
Emulsions
Hypoglycemic Agents
Polymers
Diet
In Vitro Techniques

Keywords

  • Insulin
  • PEG-PLGA
  • Nanoparticles
  • stability
  • controlled delivery
  • diabetes.

Cite this

@article{70187b49936443ff8c70aa90bdf6e6e2,
title = "Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG",
abstract = "The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10{\%} PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.",
keywords = "Insulin, PEG-PLGA, Nanoparticles, stability, controlled delivery, diabetes.",
author = "Yusuf haggag and Yasser Abdel-Wahab and Opeolu Ojo and Mohamed Osman and Sanna El-Gazawy and Mohamed El-Tanani and Ahmed Faheem and Paul McCarron",
year = "2015",
month = "12",
day = "30",
doi = "10.1016/j.ijpharm.2015.12.063",
language = "English",
volume = "499",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",

}

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG. / haggag, Yusuf; Abdel-Wahab, Yasser; Ojo, Opeolu; Osman, Mohamed; El-Gazawy, Sanna; El-Tanani, Mohamed; Faheem, Ahmed; McCarron, Paul.

In: International Journal of Pharmaceutics, Vol. 499, 30.12.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

AU - haggag, Yusuf

AU - Abdel-Wahab, Yasser

AU - Ojo, Opeolu

AU - Osman, Mohamed

AU - El-Gazawy, Sanna

AU - El-Tanani, Mohamed

AU - Faheem, Ahmed

AU - McCarron, Paul

PY - 2015/12/30

Y1 - 2015/12/30

N2 - The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.

AB - The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 hours to 6 days in type I diabetic mice.

KW - Insulin

KW - PEG-PLGA

KW - Nanoparticles

KW - stability

KW - controlled delivery

KW - diabetes.

U2 - 10.1016/j.ijpharm.2015.12.063

DO - 10.1016/j.ijpharm.2015.12.063

M3 - Article

VL - 499

JO - International Journal of Pharmaceutics

T2 - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -