Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs

Salonen, Jarno; La, Laitinen; Kaukonen, Ann Marie; Tuura, Jaani; Björkqvist, M.; Heikkilä, Teemu; Vähä-Heikkilä, Kalle; Hirvonen, Jouni; Lehto, Vesa‐Pekka

doi:10.1016/j.jconrel.2005.08.017

Cited by 496 publications

(394 citation statements)

References 21 publications

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“…15,16 Unfortunately, the instability of the underlying surface to aqueous environments has hindered the wide-scale employment of PSi for biological applications. 17,18 Recent interest in PSi was focused on its use as a delivery vehicle for therapeutic agents such as ibuprofen 19 and insulin. 20 Central to the use of PSi as an effective drug delivery system is the need to find balance between passivation of the highly reactive native Si-H x surface species to minimize damage to the loaded molecule and control the release of the drug by erosion of the PSi matrix.…”

Section: Introductionmentioning

confidence: 99%

Vapor-phase silanization of oxidized porous silicon for stabilizing composition and photoluminescence

Zhu

et al. 2009

Journal of Applied Physics

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A vapor-phase deposition approach to the silanization modification of the oxidized porous silicon ͑PSi͒ surface using ͑CH 3 O͒ 3 Si͑CH 2 ͒ 3 NH 2 has been exploited. Standard clean ͑SC͒-1 ͑NH 3 H 2 O / H 2 O 2 / H 2 O, 1:1:5,v/ v͒ and SC-2 ͓HCl/ H 2 O 2 / H 2 O ͑1:1:6,v/ v͔͒ solutions are utilized for the first time to obtain oxidized PSi and have been proved to be a very efficient combination for creating Si-OH species on the PSi surface. After the modification, an amine group terminated surface was successfully created as demonstrated by the contact angle with water, the x-ray photoelectron spectroscopy, and the Fourier transform infrared ͑FTIR͒ spectra. The influences of the surface derivatives on the composition stability of the PSi layer and on its photoluminescence properties were investigated by means of FTIR spectra, photoluminescence spectra, and time-resolved photoluminescence measurements.

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Section: Introductionmentioning

confidence: 99%

Vapor-phase silanization of oxidized porous silicon for stabilizing composition and photoluminescence

Zhu

et al. 2009

Journal of Applied Physics

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“…11 Drug and peptide delivery by PSi particles has already been demonstrated and with promising results. 12,13 PSi particles can be loaded with diverse payloads, such as small molecule drugs and peptides. In addition, improved solubility of poorly soluble drugs after loading has been reported.…”

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confidence: 99%

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

et al. 2010

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Porous silicon (PSi) particles have been studied for the effects they elicit in Caco-2 and RAW 264.7 macrophage cells in terms of toxicity, oxidative stress, and inflammatory response. The most suitable particles were then functionalized with a novel 18 F label to assess their biodistribution after enteral and parenteral administration in a rat model. The results show that thermally hydrocarbonized porous silicon (THCPSi) nanoparticles did not induce any significant toxicity, oxidative stress, or inflammatory response in Caco-2 and RAW 264.7 macrophage cells. Fluorescently labeled nanoparticles were associated with the cells surface but were not extensively internalized. Biodistribution studies in rats using novel 18 F-labeled THCPSi nanoparticles demonstrated that the particles passed intact through the gastrointestinal tract after oral administration and were also not absorbed from a subcutaneous deposit. After intravenous administration, the particles were found mainly in the liver and spleen, indicating rapid removal from the circulation. Overall, these silicon-based nanosystems exhibit excellent in vivo stability, low cytotoxicity, and nonimmunogenic profiles, ideal for oral drug delivery purposes.

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“…Elemental and molecular information were used to study their distributions in the porous region and the chemistry of their adsorption. Methylene blue (MW ϭ 284 Da) [4], and the delivery of active pharmaceutical ingredients [5,6]. The ongoing interest in pSi for use as a therapeutic delivery system is due to the large internal surface area available, the readily modified surface chemistry [7] and, in particular, the excellent in vivo biodegradation and biocompatibility (low toxicity) of the silicon substrate, hydrolysing to form orthosilicic acid, which is readily excreted [8].…”

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confidence: 99%

“…Negative fragments (SiOSH 3 Ϫ and SiO 2 SCH -) also suggested chemisorption via O bridging of the substrate Si and methylene blue S. The larger Papain molecule (23,406 Da) distributed itself in a similar manner to methylene blue demonstrating larger molecules can be effectively incorporated into such pore structures. (J Am Soc Mass Spectrom 2010, 21, 254 -260) © 2010 American Society for Mass Spectrometry P orous silicon (pSi) is a nanostructured material with 2-50 nm pores and has been investigated for use in a range of applications, including; optical [1,2], biosensing [3], radiotherapy (brachytherapy) [4], and the delivery of active pharmaceutical ingredients [5,6]. The ongoing interest in pSi for use as a therapeutic delivery system is due to the large internal surface area available, the readily modified surface chemistry [7] and, in particular, the excellent in vivo biodegradation and biocompatibility (low toxicity) of the silicon substrate, hydrolysing to form orthosilicic acid, which is readily excreted [8].…”

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confidence: 99%

Use of TOF-SIMS to study adsorption and loading behavior of methylene blue and papain in a nano-porous silicon layer

Kempson

Barnes

Prestidge

2010

J. Am. Soc. Mass Spectrom.

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TOF-SIMS was applied to study the cross-sectional distribution of methylene blue and papain in porous silicon layers. Elemental and molecular information were used to study their distributions in the porous region and the chemistry of their adsorption. Methylene blue (MW ϭ 284 Da) [4], and the delivery of active pharmaceutical ingredients [5,6]. The ongoing interest in pSi for use as a therapeutic delivery system is due to the large internal surface area available, the readily modified surface chemistry [7] and, in particular, the excellent in vivo biodegradation and biocompatibility (low toxicity) of the silicon substrate, hydrolysing to form orthosilicic acid, which is readily excreted [8]. The loading dynamics of molecules into a pSi matrix is dependent on wetting and the size of the pores. Likewise, the interaction between a loaded molecule and the pSi substrate is of interest, particularly in the case of protein based therapeutics, whose bioactivity is dependent on remaining in a specific 3D conformation.TOF-SIMS analysis provides information regarding elemental and molecular species present in a sample surface (i.e., within 1-1.5 nm) with high mass resolution (up to ϳ10,000 m/⌬m) and spatial resolution for imaging (ϳ1 micron). Molecular and elemental information is obtained for organic and inorganic materials providing a powerful technique to image organic compounds associated with inorganic substrates or vice versa [9,10]. This has been demonstrated by imaging solid-state pharmaceutical formulations [11][12][13][14], however, to date this has not been extended to porous silicon substrates.In this study, TOF-SIMS was used to map the distribution of methylene blue and papain across porous silicon layers after loading from aqueous solution. Methylene blue (C 16 H 18 N 3 S ϩ , MW ϭ 284.12 g/mol) is a relatively small organic dye molecule commonly used in adsorption studies and can be considered analogous to therapeutic molecules. A molecular mass of 284 g/mol is within a reasonable mass range for a TOF-SIMS' Ga ϩ primary ion beam and can be easily and uniquely identified without interference or confusion from spectral peaks originating from the silicon substrate or in the instance of organic contamination. This molecule was chosen for its convenience, and to assess the ability to use smaller organic fragments to reflect the distribution of the molecule of interest. This is important to be able to extend this work to studying larger molecules, such as proteins and enzymes of pharmaceutical interest, which will not provide a molecular ion in TOF-SIMS. In contrast to methylene blue, papain is a much larger molecule, detailed elsewhere [15], comprising 212 residue units in two domains, giving a molecular weight of 23,406 g/mol. Papain is a cysteine protease hydrolase enzyme present in papaya. This molecular weight is far greater than can be detected with TOF-SIMS, however, fragmentation products can be detected. Smaller organic fragments can be compared with the distribution of methylene blue to investigate si...

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Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs

Cited by 496 publications

References 21 publications

Vapor-phase silanization of oxidized porous silicon for stabilizing composition and photoluminescence

Vapor-phase silanization of oxidized porous silicon for stabilizing composition and photoluminescence

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Use of TOF-SIMS to study adsorption and loading behavior of methylene blue and papain in a nano-porous silicon layer

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