Antacid co-encapsulated polyester nanoparticles for peroral delivery of insulin: development, pharmacokinetics, biodistribution and pharmacodynamics

G. Sharma, C. F. Van Der Walle, M.N.V Ravi Kumar

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The in vitro/in vivo characterization of antacid-insulin co-encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles is presented here. The optimized nanoparticle composition has 1% surfactant (didodecyl dimethylammonium bromide) and 2% antacid (magnesium hydroxide or zinc carbonate) in the size range ∼136-143 nm with ∼81-85% entrapment of insulin at a 4% (w/w) initial load to that of polymer. Molecular characterization using circular dichroism, fluorescence and Fourier transform infrared spectroscopy showed that the structural integrity of insulin was maintained during formulation. Furthermore, the encapsulated insulin was well protected under in vitro simulated gastric and intestinal fluids. Nanoparticle insulin results in six fold increase in oral bioavailability to that of plain insulin in healthy rats. In diabetic rats, a 120 IU/kg oral dose of insulin nanoparticles achieved an equivalent blood glucose lowering effect to a 20 IU/kg subcutaneous (sc) dose of insulin solution, the nadir in blood glucose concentration occurring 24 h and 1 h post-administration, respectively. Both sc insulin and oral nanoparticle insulin partially attenuated hyperglycemia-induced inflammation caused by tumor necrosis factor α, but not by interleukin-6 or C-reactive protein; on the other hand, subcutaneous insulin was found to be more effective on lipid profile measured in the form of high density lipoprotein, cholesterol and triglyceride. Successful oral insulin could be beneficial in type II complications.

LanguageEnglish
Pages99-110
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume440
Issue number1
DOIs
Publication statusPublished - 2 Jan 2013

Fingerprint

Antacids
Polyesters
Nanoparticles
Pharmacokinetics
Insulin
Blood Glucose
Magnesium Hydroxide
Polyglactin 910
Fourier Transform Infrared Spectroscopy
Circular Dichroism
Bromides
Surface-Active Agents
Hyperglycemia
C-Reactive Protein
HDL Cholesterol
Biological Availability
Interleukin-6
Stomach
Polymers
Tumor Necrosis Factor-alpha

Keywords

  • antacid co-encapsulated
  • peroral delivery
  • polyester nanoparticles
  • insulin
  • biodistribution
  • pharmacodynamics
  • pharmacokinetics

Cite this

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abstract = "The in vitro/in vivo characterization of antacid-insulin co-encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles is presented here. The optimized nanoparticle composition has 1{\%} surfactant (didodecyl dimethylammonium bromide) and 2{\%} antacid (magnesium hydroxide or zinc carbonate) in the size range ∼136-143 nm with ∼81-85{\%} entrapment of insulin at a 4{\%} (w/w) initial load to that of polymer. Molecular characterization using circular dichroism, fluorescence and Fourier transform infrared spectroscopy showed that the structural integrity of insulin was maintained during formulation. Furthermore, the encapsulated insulin was well protected under in vitro simulated gastric and intestinal fluids. Nanoparticle insulin results in six fold increase in oral bioavailability to that of plain insulin in healthy rats. In diabetic rats, a 120 IU/kg oral dose of insulin nanoparticles achieved an equivalent blood glucose lowering effect to a 20 IU/kg subcutaneous (sc) dose of insulin solution, the nadir in blood glucose concentration occurring 24 h and 1 h post-administration, respectively. Both sc insulin and oral nanoparticle insulin partially attenuated hyperglycemia-induced inflammation caused by tumor necrosis factor α, but not by interleukin-6 or C-reactive protein; on the other hand, subcutaneous insulin was found to be more effective on lipid profile measured in the form of high density lipoprotein, cholesterol and triglyceride. Successful oral insulin could be beneficial in type II complications.",
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Antacid co-encapsulated polyester nanoparticles for peroral delivery of insulin : development, pharmacokinetics, biodistribution and pharmacodynamics. / Sharma, G.; Van Der Walle, C. F.; Ravi Kumar, M.N.V.

In: International Journal of Pharmaceutics, Vol. 440, No. 1, 02.01.2013, p. 99-110.

Research output: Contribution to journalArticle

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AB - The in vitro/in vivo characterization of antacid-insulin co-encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles is presented here. The optimized nanoparticle composition has 1% surfactant (didodecyl dimethylammonium bromide) and 2% antacid (magnesium hydroxide or zinc carbonate) in the size range ∼136-143 nm with ∼81-85% entrapment of insulin at a 4% (w/w) initial load to that of polymer. Molecular characterization using circular dichroism, fluorescence and Fourier transform infrared spectroscopy showed that the structural integrity of insulin was maintained during formulation. Furthermore, the encapsulated insulin was well protected under in vitro simulated gastric and intestinal fluids. Nanoparticle insulin results in six fold increase in oral bioavailability to that of plain insulin in healthy rats. In diabetic rats, a 120 IU/kg oral dose of insulin nanoparticles achieved an equivalent blood glucose lowering effect to a 20 IU/kg subcutaneous (sc) dose of insulin solution, the nadir in blood glucose concentration occurring 24 h and 1 h post-administration, respectively. Both sc insulin and oral nanoparticle insulin partially attenuated hyperglycemia-induced inflammation caused by tumor necrosis factor α, but not by interleukin-6 or C-reactive protein; on the other hand, subcutaneous insulin was found to be more effective on lipid profile measured in the form of high density lipoprotein, cholesterol and triglyceride. Successful oral insulin could be beneficial in type II complications.

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