Targeted Delivery of Amantadine-loaded Methacrylate Nanosphere-ligands for the Potential Treatment of Amyotrophic Lateral Sclerosis

  • Zamanzima Mazibuko Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Sunaina Indermun Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Mershen Govender Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Pradeep Kumar Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa. http://orcid.org/0000-0002-8640-4350
  • Lisa C du Toit Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Yahya E Choonara Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Girish Modi Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Dinesh Naidoo Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
  • Viness Pillay Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa. http://orcid.org/0000-0002-8119-3347

Abstract

Purpose. This study aimed to develop and analyse poly(DL-lactic acid)-methacrylic acid nanospheres bound to the chelating ligand diethylenetriaminepentaacetic acid (DTPA)  for the targeted delivery of amantadine in Amyotrophic Lateral Sclerosis (ALS). Methods. The nanospheres were prepared by a double emulsion solvent evaporation technique statistically optimized employing a 3-Factor Box-Behnken experimental design. Analysis of the particle size, zeta potential, polydispersity (Pdl), morphology, drug entrapment and drug release kinetics were carried out. Results. The prepared nanospheres were determined to have particle sizes ranging from 68.31 to 113.6 nm (Pdl 0.5). An initial burst release (50% of amantadine released in 24 hr) was also obtained, followed by a prolonged release phase of amantadine over 72 hr. Successful conjugation of the chelating ligand onto the surface of the optimised nanospheres was thereafter achieved and confirmed by TEM. The synthesized modified nanospheres were spherical in shape, 105.6 nm in size, with a PdI of 0.24 and zeta potential of -28.0 mV. Conjugation efficiency was determined to be 74%. In vitro and ex vivo cell study results confirmed the intracellular uptake of the modified nanospheres by the NSC-34 cell line and the non-cytotoxicity of the synthesized nanospheres. Conclusions. Biocompatible amantadine-loaded nanospheres were successfully designed, characterized and optimized employing the randomized Box-Behnken statistical design. Delivery of amantadine over 72 hrs was achieved, with the nanospheres being of a size capable of internalization by the NSC- 34 cells.

 

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Author Biographies

Zamanzima Mazibuko, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

PG Student

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg

Sunaina Indermun, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Postdoctoral Research Fellow
Mershen Govender, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Postdoctoral Research Fellow
Pradeep Kumar, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Dr. Pradeep Kumar (PhD, Wits)

SeniorLecturer of Pharmaceutics

Senior Researcher I Wits Advanced Drug Delivery Platform

University of the Witwatersrand I Faculty of Health Sciences 

Dept of Pharmacy and Pharmacology I 7 York Rd, Parktown, 2193 JHB, RSA

Lisa C du Toit, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Prof. Lisa Claire du Toit | Associate Professor : Pharmaceutical Chemistry

Senior Researcher : Wits Advanced Drug Delivery Platform

University of the Witwatersrand | Department of Pharmacy and Pharmacology

Yahya E Choonara, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Chairman and Head | Pharmacy and Pharmacology

Senior Scientist and Manager | Wits Advanced Drug Delivery Platform (WADDP)

University of the Witwatersrand

7 York Road, Parktown 2193

Johannesburg, South Africa

Girish Modi, Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Professor and Chief Specialist

Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,

Dinesh Naidoo, Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Neurosurgeon

Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg

Viness Pillay, Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Personal Professor of Pharmaceutics
NRF Research Chair | Director: WADDP

University of the Witwatersrand

Dept. of Pharmacy and Pharmacology
Published
2018-03-30
How to Cite
MazibukoZ., IndermunS., GovenderM., KumarP., du ToitL. C., ChoonaraY. E., ModiG., NaidooD., & PillayV. (2018). Targeted Delivery of Amantadine-loaded Methacrylate Nanosphere-ligands for the Potential Treatment of Amyotrophic Lateral Sclerosis. Journal of Pharmacy & Pharmaceutical Sciences, 21, 94-109. https://doi.org/10.18433/jpps29595
Section
Pharmaceutical Sciences; Original Research Articles