Polyglutamic Acid Functionalization of Chitosan Nanoparticles Enhances the Therapeutic Efficacy of Insulin Following Oral Administration

AAPS PharmSciTech
Dileep UrimiSanyog Jain

Abstract

In the present study, stable chitosan nanoparticles (Ch-NPs) were developed using the ionotropic gelation method, where poly(sodium 4-styrenesulfonate) (PSS) was used as a cross-linking agent while polyglutamic acid (PGA) for functionalization to improve the oral uptake through calcium-sensing receptors and amino acid transporters present in intestinal epithelium. Formulation was optimized by the design of experiments (DoE) approach using a three-level central composite design and characterized for in vitro parameters such as morphology, particle size, polydispersity index (PDI), entrapment efficiency and zeta potential. Morphological analysis demonstrated the formation of spherical NPs with particle size, zeta potential, and entrapment efficiency in the range of 210 nm ± 2.8 nm, 18.1 mV ± 0.14 mV, and 85.9% ± 0.28%, respectively. The developed NPs exhibited sustained release at different pH conditions and almost threefold higher uptake in comparison with non-functionalized NPs in Caco-2 cell uptake studies. In vivo studies in diabetic animals demonstrated low levels of plasma glucose for almost 24 h. Pharmacological availability (PA) of insulin administered through Ch-PSS-PGA NPs (17.28 ± 0.9) was significantly higher as compa...Continue Reading

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Citations

Aug 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rimesh AugustineIl Kim
Dec 7, 2020·International Journal of Biological Macromolecules·Ishneet KaurSanyog Jain
Jul 3, 2021·Nanomaterials·Francisco G BlancoM Auxiliadora Prieto
Dec 4, 2021·Drug Development Research·Adel Abdel-Moneim, Hanaa Ramadan

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Methods Mentioned

BETA
dynamic light scattering
Scanning electron microscopy
electrophoresis
circular dichroism
profiler

Software Mentioned

JMP

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