Abstract
Biodegradable porous silicon (pSi) particles are under development for drug delivery applications. The optimum particle size very much depends on medical use, and microparticles can outperform nanoparticles in specific instances. Here we demonstrate the ability of sedimentation to size-select ultrasmall (1–10 μm) nanoporous microparticles in common solvents. Size tunability is quantified for 1–24 h of sedimentation. Experimental values of settling times in ethanol and water are compared to those calculated using Stokes’ Law. Differences can arise due to particle agglomeration, internal gas generation and incomplete wetting. Air-dried and supercritically-dried pSi powders are shown to have, for example, their median diameter d (0.5) particle sizes reduced from 13 to 1 μm and from 20 to 3 μm, using sedimentation times of 6 and 2 h respectively. Such filtered microparticles also have much narrower size distributions and are hence suitable for administration in 27 gauge microneedles, commonly used in intravitreal drug delivery.
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References
Santos HA, Salonen J, Bimbo LM, Lehto V-P, Peltonen L, Hirvonen J (2011). Mesoporous materials as controlled drug delivery formulations. J Drug Del Sci Technol 2-1(2):139–155
Kennedy E, Canham L (2016). Mesoporous biomaterials: a lexicon and structured Bibliography of Reviews. HA Santos. Open Mater Sci 3:1–14
Salonen J, Kaukonen AM, Hirvonen J, Lehto VP (2008). Mesoporous silicon in drug delivery applications. J Pharm Sci 97:632–653
Nekovic E, Storey CJ, Kaplan A, Theis W, Canham LT (2020). Communication—supercritically-dried membranes and powders of >90% porosity silicon with pore volumes exceeding 4 cm3g−1. ECS J Sol State Sci Technol 9:024016
Li W, Liu Z, Fontana F, Ding Y, Liu D, Hirvonen JT, Santos HA (2018). Tailoring porous silicon for biomedical applications: from drug delivery to cancer immunotherapy. Adv Mater 30:24
Kohane DS (2007). Microparticles and nanoparticles for drug delivery. Biotechnol Bioeng 96:203–209
Lee JH, Yeo Y (2015) Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci 125:75–84
Tzur-Balter A, Rubinski A, Segal E (2013). Designing porous silicon-based microparticles as carriers for controlled delivery of mitoxantrone dihydrochloride. J Mater Res 28(2):231–239
Canham LT (2014) in Porous Silicon for Biomedical Applications, Edited by H. Santos, Woodhead Publishing, Series in Biomaterials No 88, pp 3–20
Goh AS, Chung AY, Lo RH, Lau TN, Yu SW, Chng M, Satchithanantham S, Loong SL, Ng DC, Lim BC, Connor S, Chow PK (2007). A novel approach to brachytherapy in hepatocellular carcinoma using a phosphorus 32brachytherapy delivery device – a first in man study. Intnl J Radiation Oncol Biol Phys 67(3):786–792
Warther D, Xiao Y, Li F, Wang Y, Huffman K, Freeman WR, Sailor M, Cheng L (2018) Porous silicon based intravitreal platform for dual-drug loading and controlled release towards synergistic therapy. Drug Deliv 25(1):1537–1545
Loni A (2018) In: Canham L (ed) Handbook of Porous Silicon. Springer, Cham, pp 1051–1061
Storey CJ, Nekovic E, Kaplan A, Theis W, Canham LT (2020) Preserving surface area and porosity during fabrication of silicon aerocrystal particles from anodized wafers. J Porous Mater 30(4):1–6
Puthli S, Vavia PR (2009) Stability Studies of Microparticulate System with Piroxicam as Model Drug. AAPS PharmSciTech 10(3):872–880
Miller MA, Engstrom JD, Ludher BS, Johnston KP (2010) Low Viscosity Highly Concentrated Injectable Nonaqueous Suspensions of Lysozyme Microparticles. Langmuir 26(2):1067–1074
Whitaker MA, Langston P, Naylon A, Azzopardi BJ, Howdle SM (2011) Particle size and shape effects in medical syringe needles: experiments and simulations for polymer microparticle injection. J Mater Sci Mater Med 22:1975–1983
Hon NK, Shaposhnik Z, Diebold ED, Tamanoi F, Jalali B, Biomed J (2012) Tailoring the biodegradability of porous silicon nanoparticles. Mater Res Part A 100A:3416–3421
Roberts DS, Estrada D, Yagi N, Anglin EJ, Chan NA, Sailor MJ (2017) Preparation of Photoluminescent Porous Silicon Nanoparticles by High-Pressure Microfluidization. Part Part Syst Charact 34:1600326
Litvinenko S, Alekseev S, Lysenko V, Venturello A, Geobaldo F, Gulina L, Kuznetsov G, Tolstoy V, Skryshevsky V, Garrone E, Barbier D (2010) Hydrogen production from nano-porous Si powder formed by stain etching. Int J Hydrog Energy 35:6773–6778
Vidi-Simiti IV, Jumate N, Thalmaier G, Sechel N, Moldovan V (2012). Measurement of particle density, porosity, and size distributions by sedimentation/steric field-flow fractionation: application to chromatographic supports. J. Porous Mater 19:21–27
Giddings JC, Moon MH (1991). Measurement of particle density, porosity, and size distributions by sedimentation/steric field-flow fractionation: application to chromatographic supports. Anal Chem 63:24
Philipse AP, Bonekamp BC, Veringa HJ (1990). Colloidal filtration and [simultaneous) sedimentation of alumina and silica suspensions: influence of aggregates. J Am Ceram Soc 73(9):2720–2727
Canham LT, Cullis AG, Pickering C, Dosser OD, Cox TI, Lynch TP (1994) Luminescent anodized silicon aerocrystal networks prepared by supercritical drying. Nature 368(6467):133–135
Loni A, Canham LT, Defforge T, Gautier G (2015). Supercritically-Dried Porous Silicon Powders with Surface Areas Exceeding 1000 m2/g. ECS J Solid State Sci Technol 4(8):289–292
Sediq AS, Waasdorp SKD, Nejadnik MR, van Beers MMC, Meulenaar J, Verrijk R, Jiskoot W (2017) Determination of the Porosity of PLGA Microparticles by Tracking Their Sedimentation Velocity Using a Flow Imaging Microscope (FlowCAM). Pharm Res 34:1104–1114
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EN would like to thank the School of Physics & Astronomy at the University of Birmingham for funding her doctoral research.
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This research was funded by the School of Physics & Astronomy, University of Birmingham.
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EN, CJS and LTC designed the studies; EN conducted the Stokes Law calculations; EN and CJS performed the experimental work; AK,WT and LTC managed the project. All authors contributed to writing and approving the final version of the paper.
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Nekovic, E., Storey, C.J., Kaplan, A. et al. A Gentle Sedimentation Process for Size-Selecting Porous Silicon Microparticles to Be Used for Drug Delivery Via Fine Gauge Needle Administration. Silicon 14, 589–596 (2022). https://doi.org/10.1007/s12633-020-00895-3
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DOI: https://doi.org/10.1007/s12633-020-00895-3