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Quinoline‐ n ‐butylcyanoacrylate‐based nanoparticles for brain targeting for the diagnosis of Alzheimer's disease
Author(s) -
Kulkarni Padmakar V.,
Roney Celeste A.,
Antich Peter P.,
Bonte Frederick J.,
Raghu Anjanapura V.,
Aminabhavi Tejraj M.
Publication year - 2009
Publication title -
wiley interdisciplinary reviews: nanomedicine and nanobiotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 72
eISSN - 1939-0041
pISSN - 1939-5116
DOI - 10.1002/wnan.59
Subject(s) - in vivo , chemistry , alzheimer's disease , β amyloid , pharmacology , curcumin , dementia , pathology , medicine , disease , biology , microbiology and biotechnology
A survey of research activity on nanoparticles (NPs) based on polymeric 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 125 I‐clioquinol (CQ, 5‐chloro‐7‐iodo‐8‐hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of 125 I‐CQ using the NPs of PBCA. The 125 I‐CQ discriminately binds to the AD post‐mortem brain tissue homogenates versus control. 125 I‐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 125 I‐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 125 I‐CQ. Brain retention of 125 I‐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. Fe 2+ and Cu 2+ . The 125 I‐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 125 I‐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) ( 123 I) or PET ( 124 I) 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. WIREs Nanomed Nanobiotechnol 2010 2 35–47 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease