Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor

Jessica Fernandes, M. Vivek Ghate, Sanchari Basu Mallik, Shaila A. Lewis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nanoparticles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of the formulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrier permeability of the nanoparticles was successfully demonstrated by the incorporation of fluorescent dye, Rhodamine B in the nanoparticles. In vivo studies were conducted in rats and the results showed that the nanoparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was less than the Cmax of the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAX from the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The pharmacokinetic studies demonstrated that nanoparticles had an (AUC0–t) of 3.42 times lower than the pure SAX, indicating the stability of the prepared formulation in the plasma.

Original languageEnglish
Pages (from-to)563-571
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume547
Issue number1-2
DOIs
Publication statusPublished - 25-08-2018

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Dipeptidyl-Peptidase IV Inhibitors
Chitosan
Nanoparticles
Amino Acids
Brain
rhodamine B
Blood-Brain Barrier
Drug Repositioning
Carbodiimides
saxagliptin
Valine
Enzyme Inhibitors
Fluorescent Dyes
Particle Size
Blood Glucose
Permeability
Alzheimer Disease
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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abstract = "Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nanoparticles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of the formulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrier permeability of the nanoparticles was successfully demonstrated by the incorporation of fluorescent dye, Rhodamine B in the nanoparticles. In vivo studies were conducted in rats and the results showed that the nanoparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was less than the Cmax of the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAX from the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The pharmacokinetic studies demonstrated that nanoparticles had an (AUC0–t) of 3.42 times lower than the pure SAX, indicating the stability of the prepared formulation in the plasma.",
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Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor. / Fernandes, Jessica; Ghate, M. Vivek; Basu Mallik, Sanchari; Lewis, Shaila A.

In: International Journal of Pharmaceutics, Vol. 547, No. 1-2, 25.08.2018, p. 563-571.

Research output: Contribution to journalArticle

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