TY - GEN
T1 - Design of a novel PAMAM-Based nanomedicine with sustained NAC release for treatment of neuroinflammation
AU - Gok, Ozgul
AU - Kambhampati, Siva P.
AU - Smith, Elizabeth
AU - Kannan, Sujatha
AU - Kannan, Rangaramanujam M.
N1 - Funding Information:
This study was funded by NIBIB R01EB018306 project and TUBITAK 2219 post-doctoral scholarship.
Publisher Copyright:
© 2017 IEEE.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
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U2 - 10.1109/BIYOMUT.2017.8479287
DO - 10.1109/BIYOMUT.2017.8479287
M3 - Conference contribution
AN - SCOPUS:85056415897
T3 - 2017 21st National Biomedical Engineering Meeting, BIYOMUT 2017
BT - 2017 21st National Biomedical Engineering Meeting, BIYOMUT 2017
PB - Institute of Electrical and Electronics Engineers Inc.
T2 - 21st National Biomedical Engineering Meeting, BIYOMUT 2017
Y2 - 24 November 2017 through 26 November 2017
ER -