Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs
Introduction
The application of nanotechnology in biomedical research carries tremendous potential for drug administration. While most of the research has been focused on diagnostic systems (lab-on-chip), interest in microdevices for therapeutic applications has also increased [1], [2]. Initially, therapeutic applications of silicon-based systems were directed towards implanted devices [3], [4], with other administration routes, such as oral delivery emerging [5]. Recent reports on the advantages of mesoporous materials as drug delivery vehicles have encouraged research in novel applications, supporting also conventional dosage forms, and several potential materials for this purpose have been reported [6], [7], [8], [9].
Main efforts in the studies of mesoporous materials as drug delivery vehicles have been focused on sustained/controlled drug release [7], [8], [9]. The potential of mesoporous materials to improve the permeability of large, hydrophilic drug substances has also been explored in combination with classical permeation enhancers [6]. Further, mesoporous materials offer a potential means to increase the dissolution of poorly soluble drug via effects on surface area or crystallinity. At pore sizes only a few times larger than the drug molecule, the formation of crystalline material is restricted by the confined space of the pores, thus retaining the drug in its noncrystalline, amorphous form. The amorphous form is known to exhibit higher dissolution rates than the crystalline phase, especially when solubility is limited by high crystal energy [10]. Drug delivery strategies providing the potential to tailor the physical state of a compound will be of increasing importance in drug development, since it is estimated that 40% of potential lead candidates suffer from poor solubility, a great part of which may be related to high crystal energy [11].
Porous silicon (PSi) has some advantages compared to synthesised mesoporous materials when drug delivery vehicles are considered. The fabrication of PSi is a simple procedure, where the porosity and pore size can easily be tuned by anodization parameters [12]. Depending on the morphology, PSi could be tailored as a biodegradable, bioactive or stable material [13], [14]. In addition, the surface chemistry of PSi can easily be modified to produce surfaces favourable for drug adsorption [15], [16]. In this work, we will describe a simple fabrication method to produce mesoporous silicon microparticles with a surface stabilisation suitable for oral drug administration applications. Five model drugs, antipyrine, ibuprofen, griseofulvin, ranitidine and furosemide, were used to study drug loading into the microparticles and subsequent drug release behaviour. The compounds were chosen to represent a wide range of solubilities with additional differences in acid/base character and lipophilicity, while also representing drugs of different biopharmaceutical classification (BCS) (Table 1) [17]. Dissolution was studied at the pH-values 5.5, 6.8 and 7.4 representative of different parts of the small intestine.
Section snippets
Materials
Silicon wafers Si (100), of p+-type with resistivity values of 0.015–0.025 Ω cm were used in the preparation of porous silicon (PSi). The PSi was prepared by anodizing the wafers in an HF (38%)–ethanol mixture (HF : EtOH, 1 : 1); the process was performed in darkness. A current density of 50 mA/cm2 was used to obtain a porosity of about 60%. Free-standing films were obtained by abruptly increasing the current. The model drugs antipyrine, ibuprofen, griseofulvine, ranitidine hydrochloride, and
Results and discussion
The possibility to stabilise and optimise the surface chemistry of the mesoporous silicon microparticles is crucial for drug delivery applications. It determines the hygroscopic nature of the particles and their stability in the presence of drug loading solutions or physiological fluids [22]. In as-anodized PSi, the hydrogen-terminated surface is hydrophobic and oxidizes easily even at room temperature, leading to continuous changes in its structure and properties [23]. Thermal oxidation is one
Conclusions
The surface properties form an essential aspect in the design of porous silicon particles to be used in drug delivery. The presently used types of surface treatments, thermal carbonization (TCPSi) and thermal oxidation (TOPSi), showed that in addition to effects regarding the stability of the particles in the presence of aqueous or organic solvents, surface properties will significantly affect compound affinity towards the particle. This suggests the potential to tailor the surface properties
Acknowledgements
The financial support from the Finnish Academy of Science and Letters and from the Academy of Finland is acknowledged (grant no. 211048 and 202258).
References (26)
- et al.
BioMEMS for drug delivery
Curr. Opin. Solid State Mater. Sci.
(2002) - et al.
Bioadhesive microdevices with multiple reservoirs: a new platform for oral drug delivery
J. Control. Release
(2002) - et al.
Mesoporous SBA-15 HPLC evaluation for controlled gentamicin drug delivery
J. Control. Release
(2004) - et al.
Thermal carbonization of porous silicon surface by acetylene
J. Appl. Phys.
(2002) - et al.
A controlled release microchip
Nature
(1999) - et al.
Nanoporous biocapsules for the encapsulation of insulinoma cells: biotransport and biocompatibility considerations
IEEE Trans. Biomed. Eng.
(2001) - et al.
Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Coco-2 cell monolayer
Pharm. Res.
(2003) - et al.
Drug delivery devices based on mesoporous silicate
Drug Deliv.
(2004) - et al.
MCM-41 organic modification as drug delivery rate regulator
Chem. Mater.
(2003)
What is the true solubility advantage for amorphous pharmaceuticals?
Pharm. Res.
In search of a single solution for complex molecules
Scrip Mag.
Advancing new drug delivery concepts to gain the lead
Drug Deliv. Technol.
Effects of fabrication parameters on porous p+-type silicon morphology
Phys. Status Solidi, A Appl. Res.
Cited by (491)
Preparation and evaluation of proliposomes formulation for enhancing the oral bioavailability of ginsenosides
2024, Journal of Ginseng ResearchA pH-sensitive silica nanoparticles for colon-specific delivery and controlled release of catechin: Optimization of loading efficiency and in vitro release kinetics
2024, European Journal of Pharmaceutical SciencesPLGA and PEG based porous microparticles as vehicles for pulmonary somatropin delivery
2023, European Journal of Pharmaceutics and BiopharmaceuticsOrdered mesoporous silica nanocarriers: An innovative paradigm and a promising therapeutic efficient carrier for delivery of drugs
2023, Journal of Drug Delivery Science and Technology