title: Functionalized Nanolipobubbles Embedded Within a Nanocomposite Hydrogel: a Molecular Bio-imaging and Biomechanical Analysis of the System.
abstract: The purpose of this study was to explore the use of molecular bio-imaging systems and biomechanical dynamics to elucidate the fate of a nanocomposite hydrogel system prepared by merging FITC-labeled nanolipobubbles within a cross-linked hydrogel network. The nanocomposite hydrogel system was characterized by size distribution analysis and zeta potential as well as shears thinning behavior, elastic modulus (G'), viscous loss moduli (G"), TEM, and FTIR. In addition, molecular bio-imaging via Vevo ultrasound and Cell-viZio techniques evaluated the stability and distribution of the nanolipobubbles within the cross-linked hydrogel. FITC-labeled and functionalized nanolipobubbles had particle sizes between 135 and 158 nm (PdI = 0.129 and 0.190) and a zeta potential of -34 mV. TEM and ultrasound imaging revealed the uniformity and dimensional stability of the functionalized nanolipobubbles pre- and post-embedment into the cross-linked hydrogel. Biomechanical characterization of the hydrogel by shear thinning behavior was governed by the polymer concentration and the cross-linker, glutaraldehyde. Ultrasound analysis and Cell-viZio bio-imaging were highly suitable to visualize the fluorescent image-guided nanolipobubbles and their morphology post-embedment into the hydrogel to form the NanoComposite system. Since the nanocomposite is intended for targeted treatment of neurodegenerative disorders, the distribution of the functionalized nanolipobubbles into PC12 neuronal cells was also ascertained via confocal microscopy. Results demonstrated effective release and localization of the nanolipobubbles within PC12 neuronal cells. The molecular structure of the synthetic surface peptide remained intact for an extended period to ensure potency for targeted delivery from the hydrogel ex vivo. These findings provide further insight into the properties of nanocomposite hydrogels for specialized drug delivery.
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: Maluta S
authors.initials: MS
authors.lastname: Mufamadi
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: 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, Private Bag 3, Wits 2050, 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. viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D053761:Nanocomposites / Q000737:chemistry*; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D016650:Fluorescein-5-isothiocyanate
keywords: bio-imaging analysis; cross-linked hydrogel network; drug delivery; nanocomposite system; nanolipobubbles