Design of a novel PAMAM-Based nanomedicine with sustained NAC release for treatment of neuroinflammation

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

PAMAM dendrimers have recently been utilized as promising biomaterials for intrinsically targeting the brain in CNSrelated disorders with no effective therapies, such as cerebral palsy (CP) and ischemia. Previous studies have established their ability to penetrate the blood-brain barrier (BBB) and diffuse freely within the brain parenchyma, which are the primary challenges. In addition, PAMAM dendrimers have been shown to selectively localize to activated microglia and astrocytes in regions of neuroinflammation, allowing for efficient delivery of potent therapeutics to sites of injury. In this study, a novel PAMAM-based drug delivery system for the anti-inflammatory small molecule N-acetyl cysteine (NAC) as a brain targeting nano-vehicle with a sustained and slow drug release profile is presented. This design enables NAC molecules conjugated to the periphery of PAMAM dendrimers with ester and disulfide linkers to release in a step-wise manner by responding to different enviromental conditions. Moreover, cellular internalization studies were conducted with a fluorescently labelled version of the conjugate to confirm nontoxicity and time-dependent cellular uptake by activated microglia. Sustained release of NAC molecules results in improved anti-inflammatory and anti-oxidative efficacies, demonstrating that D-(NAC-NAC) is a very promising drug loaded nanoparticle for prolonged treatment of CNS-related disorders.

Original languageEnglish (US)
Title of host publication2017 21st National Biomedical Engineering Meeting, BIYOMUT 2017
PublisherInstitute of Electrical and Electronics Engineers Inc.
ISBN (Electronic)9781538653401
DOIs
StatePublished - Oct 1 2018
Event21st National Biomedical Engineering Meeting, BIYOMUT 2017 - Istanbul, Turkey
Duration: Nov 24 2017Nov 26 2017

Publication series

Name2017 21st National Biomedical Engineering Meeting, BIYOMUT 2017

Other

Other21st National Biomedical Engineering Meeting, BIYOMUT 2017
CountryTurkey
CityIstanbul
Period11/24/1711/26/17

ASJC Scopus subject areas

  • Signal Processing
  • Biomedical Engineering
  • Instrumentation

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