Medical Bionics - Research Publications

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    Gel-Mediated Electrospray Assembly of Silica Supraparticles for Sustained Drug Delivery
    Ma, Y ; Bjoernmalm, M ; Wise, AK ; Cortez-Jugo, C ; Revalor, E ; Ju, Y ; Feeney, OM ; Richardson, RT ; Hanssen, E ; Shepherd, RK ; Porter, CJH ; Caruso, F (AMER CHEMICAL SOC, 2018-09-19)
    Supraparticles (SPs) composed of smaller colloidal particles provide a platform for the long-term, controlled release of therapeutics in biomedical applications. However, current synthesis methods used to achieve high drug loading and those involving biocompatible materials are often tedious and low throughput, thereby limiting the translation of SPs to diverse applications. Herein, we present a simple, effective, and automatable alginate-mediated electrospray technique for the assembly of robust spherical silica SPs (Si-SPs) for long-term (>4 months) drug delivery. The Si-SPs are composed of either porous or nonporous primary Si particles within a decomposable alginate matrix. The size and shape of the Si-SPs can be tailored by controlling the concentrations of alginate and silica primary particles used and key electrospraying parameters, such as flow rate, voltage, and collector distance. Furthermore, the performance (including drug loading kinetics, loading capacity, loading efficiency, and drug release) of the Si-SPs can be tuned by changing the porosity of the primary particles and through the retention or removal (via calcination) of the alginate matrix. The structure and morphology of the Si-SPs were characterized by electron microscopy, dynamic light scattering, N2 adsorption-desorption analysis, and X-ray photoelectron spectroscopy. The cytotoxicity and degradability of the Si-SPs were also examined. Drug loading kinetics and loading capacity for six different types of Si-SPs, using a model protein drug (fluorescently labeled lysozyme), demonstrate that Si-SPs prepared from primary silica particles with large pores can load significant amounts of lysozyme (∼10 μg per SP) and exhibit sustained, long-term release of more than 150 days. Our experiments show that Si-SPs can be produced through a gel-mediated electrospray technique that is robust and automatable (important for clinical translation and commercialization) and that they present a promising platform for long-term drug delivery.
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    Mesoporous Silica Supraparticles for Sustained Inner-Ear Drug Delivery
    Wang, Y ; Maina, JW ; Caruso, F ; Wise, AK ; Shepherd, RK ; Tan, J (Wiley, 2014)
    Mesoporous silica supraparticles (MS-SPs) are prepared via self-assembly of mesoporous silica nanoparticles under capillary force action in confined droplets. The MS-SPs are effective carriers for sustained drug delivery. Animal studies show that these particles are suitable for chronic intracochlear implantation, and neurotrophins released from the MS-SPs can efficiently rescue primary auditory neurons in an in vivo sensorineural hearing loss model.
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    Mold-Templated Inorganic-Organic Hybrid Supraparticles for Code livery of Drugs
    Maina, JW ; Cui, J ; Bjoernmalm, M ; Wise, AK ; Shepherd, RK ; Caruso, F (AMER CHEMICAL SOC, 2014-11)
    This paper reports a facile and robust mold-templated technique for the assembly of mesoporous silica (MS) supraparticles and demonstrates their potential as vehicles for codelivery of brain-derived neurotrophic factor (BDNF) and dexamethasone (DEX). The MS supraparticles are assembled using gelatin as a biodegradable adhesive to bind and cross-link the particles. Microfabricated molds made of polydimethylsiloxane are used to control the size and shape of the supraparticles. The obtained mesoporous silica-gelatin hybrid supraparticles (MSG-SPs) are stable in water as well as in organic solvents, such as dimethyl sulfoxide, and efficiently coencapsulate both BDNF and DEX. The MSG-SPs also exhibit sustained release kinetics in simulated physiological conditions (>30 days), making them potential candidates for long-term delivery of therapeutics to the inner ear.
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    Drug delivery: mesoporous silica supraparticles for sustained inner-ear drug delivery (small 21/2014).
    Wang, Y ; Wise, AK ; Tan, J ; Maina, JW ; Shepherd, RK ; Caruso, F (Wiley, 2014-11)
    Mesoporous silica supraparticles (MS-SPs) self-assembled from mesoporous silica nanoparticles are reported on page 4244 by F. Caruso and co-workers. The MS-SPs are effective carriers for the sustained delivery of brain-derived neurotrophic factor. Animal studies show that the MS-SPs can be implanted into the cochlea and deliver neurotrophins to prevent the progressive loss of the auditory neurons that normally occurs with deafness.