title: Development and in vivo evaluation of an implantable nano-enabled multipolymeric scaffold for the management of AIDS dementia complex (ADC).
abstract: This study reports the use of biocompatible and biodegradable polymers for the formulation and design of an implantable multipolymeric drug delivery device (MDDD) for the management of AIDS dementia complex (ADC), a debilitating condition affecting the cognitive, motor and behavioral systems in HIV+ individuals. A 3-factor Box-Behnken statistical design was employed for the optimization of nanoparticle and multipolymeric scaffold formulations. Fifteen formulations were generated using the Box-Behnken template, which were assessed for physicochemical and physicomechanical characterization. The optimised nanoparticle formulation yielded nanoparticles measuring 68.04nm in size and zeta potential (ZP) of -13.4mV was calculated for the colloidal system. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a multipolymeric matrix. Matrix erosion was calculated at 28% for multipolymeric scaffold and a matrix resilience of 4.451% was observed 30 days post exposure to PBS, indicating slow degradation of the MDDD. In vivo studies showed 12.793ng/mL and 35.225ng/mL AZT level in plasma and CSF. In view of the physicomechanical properties, in vitro and in vivo drug release kinetics of MDDD makes it a potential candidate for the management of the ADC.
authors.affiliation: 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.
authors.forename: Sheri-Lee
authors.initials: SL
authors.lastname: Harilall
authors.affiliation: 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.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.affiliation: 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.
authors.forename: Lomas Kumar
authors.initials: LK
authors.lastname: Tomar
authors.affiliation: 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.
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.affiliation: 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.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 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.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.affiliation: Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.affiliation: Department of Neurosurgery, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
authors.affiliation: School of Chemical and Metallurgical Engineering, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Iyuke
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Danckwerts
authors.affiliation: 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. Electronic address: viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001921:Brain / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000295:instrumentation; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D054457:Tissue Scaffolds; D015215:Zidovudine / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D015215:Zidovudine
keywords: AIDS dementia complex management; Implantable device; Nanoparticles; Polymeric scaffold