Synthesis and characterization of chemical engineered PLGA nanosphere: Triggering mechanism of Catechol-O-methyltransferase inhibition on in vivo neurodegeneration

K Poonkuzhali; R Seenivasagan; J Prabhakaran; A Karthika

doi:10.1016/j.bioorg.2023.106673

Synthesis and characterization of chemical engineered PLGA nanosphere: Triggering mechanism of Catechol-O-methyltransferase inhibition on in vivo neurodegeneration

Bioorg Chem. 2023 Oct:139:106673. doi: 10.1016/j.bioorg.2023.106673. Epub 2023 Jun 16.

Authors

K Poonkuzhali¹, R Seenivasagan², J Prabhakaran³, A Karthika⁴

Affiliations

¹ Bioprocess and Microbial Laboratory, Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry - 605 014, India. Electronic address: biopoo23@gmail.com.
² Department of Biotechnology, Arulmigu Kalasalingam College of Arts and Science, Krishnankoil - 626126, Tamil Nadu, India.
³ Organic Synthesis Laboratory, Department of Chemistry, School of Physical, Chemical and Applied Sciences, Pondicherry University, Pondicherry - 605 014, India.
⁴ Department of Microbiology, The Standard Fireworks Rajaratnam College for Women, Sivakasi - 626123, Tamil Nadu, India.

PMID: 37354660
DOI: 10.1016/j.bioorg.2023.106673

Abstract

Chemically engineered PLGA nanospheres are one of the emerging technologies for treating neurodegenerative disorders by inhibiting Catechol-O-methyltransferase (COMT). PLGA-MATPM nanospheres were chemically synthesized using PLGA and MATPM (N-allyl-N-(3-(m-tolyloxy)propyl) methioninate). The tailored PLGA nanospheres induce dose-dependent COMT inhibition in competitive kinetic mode. The interactions between COMT and PLGA nanosphere are explained by spectroscopic and molecular dynamics analysis. PLGA-MATPM NPs suppressed the growth of neuroblastoma cells due to the neurodegenerative toxicity of MPTP induction, demonstrating its potency as a cure for neurological disorders. PLGA-MATPM NPs cross the blood-brain barrier more effectively than those in the blood. Furthermore, PLGA nanospheres showed the most neurodegenerative recovery against MPTP-induced C57BL/6 mice. Using magnetic resonance imaging (MRI), it was validated for quality images of cerebral blood flow (CBF).

Keywords: Catechol-O-methyltransferase; Enzyme kinetics; MR imaging; Neuroblastoma; PLGA nanosphere.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catechol O-Methyltransferase Inhibitors / pharmacology
Catechol O-Methyltransferase* / metabolism
Methylation
Mice
Mice, Inbred C57BL
Nanospheres* / chemistry

Substances

Catechol O-Methyltransferase
Catechol O-Methyltransferase Inhibitors