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Surface-Engineered Nanoliposomes by Chelating Ligands for Modulating the Neurotoxicity Associated with β-Amyloid Aggregates of Alzheimer’s disease

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Abstract

Purpose

To develop chelating ligand-bound nanoliposomes (NLPs) for the prevention and reversal of β-Amyloid (Aβ) aggregation associated with promoting neurotoxicity in Alzheimer disease (AD).

Methods

Four different chelating ligands (CuAc, EDTA, histidine and ZnAc) were surface-engineered onto NLPs using either covalent or non-covalent conjugation. Successful conjugation of chelating ligands onto the surface of NLPs was confirmed by characterization studies: SEM, TEM and FTIR analysis. Chelation energetics of EDTA with Cu(II)/Zn(II)-Aβ(10-21) and nanoformation of emulsified polymers were computed and corroborated with experimental and analytical data using chemometric molecular modeling.

Results

The modified NLPs produced were spherical in shape, 127–178 nm in size, with polydispersity index from 0.217–0.920 and zeta potential range of −9.59 to −37.3 mV. Conjugation efficiencies were 30–76 %, which confirmed that chelating ligands were attached to the NLP surface.

Conclusions

In vitro and ex vivo results elucidated the effectiveness of chelating ligand-bound NLPs for prevention of CuAβ(1-42) or ZnAβ(1-42) aggregate buildup associated with neurotoxicity in PC12 neuronal cells, as well as promotion of intracellular uptake in the presence of Cu(II) or Zn(II) metal ions.

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Authors and Affiliations

  1. Faculty of Health Sciences, Dept. of Pharmacy & Pharmacology, University of the Witwatersrand, Parktown, 2193, Johannesburg, South Africa

    Maluta S. Mufamadi, Yahya E. Choonara, Pradeep Kumar, Lisa C. du Toit & Viness Pillay

  2. Faculty of Health Sciences, Dept. of Neurology, University of the Witwatersrand, Parktown, 2193, Johannesburg, South Africa

    Girish Modi

  3. Faculty of Health Sciences, Dept. of Neurosurgery, University of the Witwatersrand, Parktown, 2193, Johannesburg, South Africa

    Dinesh Naidoo

  4. School of Pharmacy & Pharmaceutical Sciences, St. John’s University of Tanzania,, Dodoma, Tanzania

    Valence M. K. Ndesendo

  5. School of Chemical & Metallurgical Engineering, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa

    Sunny E. Iyuke

Authors
  1. Maluta S. Mufamadi
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  2. Yahya E. Choonara
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  4. Girish Modi
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  5. Dinesh Naidoo
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  6. Valence M. K. Ndesendo
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  7. Lisa C. du Toit
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  8. Sunny E. Iyuke
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  9. Viness Pillay
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Correspondence to Viness Pillay.

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Mufamadi, M.S., Choonara, Y.E., Kumar, P. et al. Surface-Engineered Nanoliposomes by Chelating Ligands for Modulating the Neurotoxicity Associated with β-Amyloid Aggregates of Alzheimer’s disease. Pharm Res 29, 3075–3089 (2012). https://doi.org/10.1007/s11095-012-0770-0

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  • DOI: https://doi.org/10.1007/s11095-012-0770-0

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