Amino acid Conjugated Chitosan Nanoparticles for the Brain Targeting of Amodel Dipeptidyl Peptidase-4 Inhibitor

Fernandes, Jessica and Ghate, Vivek M and Mallik, Sanchari Basu and Lewis, Shaila A (2018) Amino acid Conjugated Chitosan Nanoparticles for the Brain Targeting of Amodel Dipeptidyl Peptidase-4 Inhibitor. International Journal of Pharmaceutics, 547. pp. 563-571. ISSN 0378-5173

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Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in thetherapy of Alzheimer’s disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier bythe conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in theblood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized bycarbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nano-particles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of theformulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrierpermeability 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 na-noparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was lessthan the Cmaxof the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAXfrom the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The phar-macokinetic 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.

Item Type: Article
Uncontrolled Keywords: Chitosanl-valine; Carbodiimide; Saxagliptin; Brain delivery; Rhodamine B
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutics
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 08 Aug 2018 05:41
Last Modified: 08 Aug 2018 05:41

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