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

Zamanzima Mazibuko1, Sunaina Indermun1, Mershen Govender1, Pradeep Kumar1, Lisa C du Toit1, Yahya E Choonara1, Girish Modi2, Dinesh Naidoo3, Viness Pillay1

1Wits 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.
2Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
3Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

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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J Pharm Pharm Sci, 21 (0): 94-109, 2018

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DOI: http://dx.doi.org/10.18433/jpps29595

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