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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Insulin-loaded PLGA microspheres for glucose-responsive release.

Jun-Zi Wu1, Gareth R Williams2, He-Yu Li1

  • 1a College of Chemistry, Chemical Engineering and Biotechnology , Donghua University , Shanghai , P.R. China.

Drug Delivery
|October 5, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed novel multilayer microspheres for diabetes treatment. These glucose-sensitive, biocompatible systems effectively control blood sugar levels in diabetic mice for over 18 days.

Keywords:
Porous microspheresglucose sensitivelayer-by-layersmart drug delivery systemsustained release

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Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Nanotechnology

Background:

  • Diabetes mellitus is a chronic metabolic disorder requiring effective blood glucose management.
  • Current insulin delivery methods face challenges in achieving sustained and responsive release.
  • Advanced drug delivery systems are crucial for improving therapeutic outcomes in diabetes.

Purpose of the Study:

  • To develop novel multilayer microspheres for glucose-responsive insulin delivery.
  • To investigate the characteristics, loading capacity, and release kinetics of the developed microspheres.
  • To evaluate the in vitro and in vivo efficacy and safety of the microspheres for diabetes treatment.

Main Methods:

  • Preparation of porous poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with insulin.
  • Coating of PLGA microspheres with alternating layers of poly(vinyl alcohol) (PVA) and a boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)].
  • Characterization of microsphere morphology, insulin loading/encapsulation efficiency, in vitro glucose-responsive release, and in vitro/in vivo toxicology.
  • Assessment of blood glucose control in diabetic mice over 18 days.

Main Results:

  • Successfully fabricated multilayer microspheres with a porous PLGA core and multilayer coating.
  • Achieved high insulin loading capacity (2.83 ± 0.15%) and encapsulation efficiency (82.6 ± 5.1%).
  • Demonstrated glucose-responsive insulin release and effective blood glucose control in diabetic mice for over 18 days.
  • Confirmed safety and high biocompatibility through in vitro and in vivo toxicology tests.

Conclusions:

  • The developed multilayer microspheres exhibit excellent glucose-responsive insulin release properties.
  • These novel microspheres are safe, biocompatible, and demonstrate significant potential for long-term diabetes management.
  • The system represents a promising smart drug-delivery platform for treating diabetes.