Quinoline-n-butylcyanoacrylate-based nanoparticles for brain targeting for the diagnosis of Alzheimer's disease

Padmakar V. Kulkarni, Celeste A. Roney, Peter P. Antich, Frederick J. Bonte, Anjanapura V. Raghu, Tejraj M. Aminabhavi

Research output: Contribution to journalReview article

82 Scopus citations

Abstract

A survey of research activity on nanoparticles (NPs) based onpolymeric devices that could cross the blood-brain barrier (BBB) is given along with the presentation of our own data on the development of NPs of n-butyl-2- cyanoacrylate (BCA) for brain delivery to aid the early diagnosis of Alzeimer's disease (AD), a neurodegenerative disorder of the elderly people, the most prevalent form of dementia. Typical data are presented on in vivo detection of amyloid peptides (Aβ) (amyloid plaques) that are used as targets for developing the biological markers for the diagnosis of AD. In order to develop efficient in vivo probes, polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated with the radio-labeled amyloid affinity drug 125I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of 125I-CQ using the NPs of PBCA. The 125I-CQ discriminately binds to the AD post-mortem brain tissue homogenates versus control. 125I-CQ-PBCA NPs labeled the Aβ plaques from the AD human post-mortem frontal cortical sections on paraffin-fixed slides. Storage phosphor imaging verified preferential uptake by AD brain sections compared to cortical control sections. The 125I-CQ-PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake measured in terms of % ID/g i.e., injected dose compared to 125I-CQ. Brain retention of 125I-CQ-PBCA NPs was significantly increased in the AD transgenic mice (APP/PS1) and in mice injected with aggregated Aβ42 peptide versus age-matched wild type controls. The results of this study are verified by in vivo storage phosphor imaging and validated by histopathological staining of plaques and select metal ions, viz. Fe2+ and Cu2+. The 125I-CQ-PBCA NPs had more efficient brain entry and rapid clearance in normal mice and enhanced the retention in AD mouse brain demonstrating the ideal in vivo imaging characteristics. The 125I-CQ-PBCA NPs exhibited specificity for Aβ plaques both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs as the promising delivery vehicle for in vivo single photon emission tomography (SPECT) (123I) or PET (124I) amyloid imaging agent. The importance of the topic in relation to brain delivery and other similar type of work published in this area are covered to highlight the importance of this research to medical disciplines .

Original languageEnglish (US)
Pages (from-to)35-47
Number of pages13
JournalWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology
Volume2
Issue number1
DOIs
StatePublished - Feb 19 2010

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

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