Impact of the strategy adopted for drug loading in nonporous silica nanoparticles on the drug release and cytotoxic activity (original) (raw)
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Nano Letters, 2009
We apply mesoporous thin silica films with nanometer-sized pores as drug carriers and incorporate the widely used anticancer drug Doxorubicin. Through single-molecule based measurements, we gain mechanistic insights into the drug diffusion inside the mesoporous film, which governs the drug-delivery at the target-site. Drug dynamics inside the nanopores is controlled by pore size and surface modification. The release kinetics is determined and live-cell measurements prove the applicability of the system for drug-delivery. This study demonstrates that mesoporous silica nanomaterials can provide solutions for current challenges in nanomedicine.
Molecules
The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluat...
International Journal of Molecular Sciences
Due to their structural, morphological, and behavioral characteristics (e.g., large volume and adjustable pore size, wide functionalization possibilities, excellent biocompatibility, stability, and controlled biodegradation, the ability to protect cargoes against premature release and unwanted degradation), mesoporous silica particles (MSPs) are emerging as a promising diagnostic and delivery platform with a key role in the development of next-generation theranostics, nanovaccines, and formulations. In this study, MSPs with customized characteristics in-lab prepared were fully characterized and used as carriers for doxorubicin (DOX). The drug loading capacity and the release profile were evaluated in media with different pH values, mimicking the body conditions. The release data were fitted to Higuchi, Korsmeyer–Peppas, and Peppas–Sahlin kinetic models to evaluate the release constant and the mechanism. The in vitro behavior of functionalized silica particles showed an enhanced cyto...
Biphenyl Wrinkled Mesoporous Silica Nanoparticles for pH-Responsive Doxorubicin Drug Delivery
Materials, 2020
Biphenyl wrinkled mesoporous silica nanoparticles with controlled particle size and high surface area were evaluated for the storage and delivery of doxorubicin. The average particle size and surface area were ~70 nm and ~1100 m2/g. The doxorubicin loading efficiency was 38.2 ± 1.5 (w/w)% and the release was pH dependent. The breast cancer cell line, MCF-7 (Michigan Cancer Foundation-7) was used for the in vitro drug release study. The cytotoxicity of doxorubicin-loaded nanoparticles was significantly higher than free doxorubicin. Fluorescence images showed biphenyl wrinkled mesoporous silica (BPWS) uptake by the MCF-7 cells. The biphenyl bridged wrinkled silica nanoparticles appear promising for hydrophobic drug loading and delivery.
Doxorubicin Loaded Silica Nanotubes : An Investigation of the Release Behavior
2015
This study aimed to investigate the release behavior of doxorubicin(DOX) from nanostructured silica tubes as carrier. The nanostructured silica nanotubes were synthesized according to the sol-gel method using tetraethoxysilane (TEOS) as silica precursor in the presence of cetyl trimethylammonium bromide (CTAB) and D-sorbitol derived organogelator as structure directing agents. The silica nanotubes were successfully prepared and their morphology has been examined with scanning electron microscopy (SEM). The release of doxorubicin was carried out by using two different release media, of pH values 7.4 and 5.5 respectively. The release was carried out by using HPLC system and the results have been reported indicating the difference in the release behavior between these two different pH media.
Korean Journal of Chemical Engineering, 2018
Mesoporous silica nanoparticles (MSNs) conjugating doxorubicin (DOX) via a pH-sensitive cleavable linkage, hydrazine (HYD) were synthesized. MSN-HYD-DOX were encapsulated with the polyaspartamide (PASPAM) grafted with the hydrophilic o-(2-aminoethyl)-o'-methylpoly(ethylene glycol) (PEG) and the cell permeating ligand, biotin (Biotin). The chemical structure of the synthesized MSN-HYD-DOX and PASPAM-g-PEG/Biotin was confirmed using FT-IR and 1 H-NMR spectroscopy. The mean diameter of the MSN-HYD-DOX@PASPAM-g-PEG/Biotin nanoparticle was 142 nm and 121 nm, respectively, examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The HYD bond was effectively cleaved in acidic condition, and thus DOX was released much faster at pH 5.0 than at pH 7.4. The cell viability in MSN-HYD-DOX@PASPAM-g-PEG/Biotin system was much lower than that of the free DOX drug because of efficient intracellular drug delivery associated with the biotin ligand.
Bioactive silica-based drug delivery systems containing doxorubicin hydrochloride: In vitro studies
Colloids and Surfaces B: Biointerfaces, 2012
This study reports the applicability of sol-gel derived silica and silica-polydimethylsiloxane (silica-PDMS) composites as a potential bioactive implantable drug delivery system for doxorubicin hydrochloride (DOX). These composites also contain calcium chloride (CaCl 2) and triethylphosphate as precursors of Ca 2+ and (PO 4) 3− ions. These composites were immersed for 20 days in a simulated body fluid (SBF) at 37 • C to study the release rate of the DOX, dissolution of the silica and the formation of hydroxyapatite on the composites' surface. The results show that the release rate of the DOX can be effectively tailored by either the addition of a polydimethylsiloxane (PDMS), or by varying the amount of CaCl 2 , where the elution rate of DOX increases with increasing amount of the CaCl 2 precursor. Importantly, irrespective of the amount of CaCl 2 , no burst release of DOX has been observed in any of the silica-PDMS system investigated. On the other hand, a slow release of DOX has been observed with a trend that followed a zero (0)-order kinetics for a total of 20 days of elusion. The dissolution of silica in SBF was ca. two-times faster than that of silica-PDMS, with the former reaching an average saturation level of 80 g/mL whilst the latter reached 46 g/mL within 20 days. Both the silica and the silica-PDMS composites show bioactivity i.e. they absorb calcium phosphate from SBF. Within 10 days, a tenfold increase in the concentration of calcium phosphate deposit has been observed on the silica-PDMS relative to the silica. The constant rates of DOX release observed for the silica-PDMS composites indicate that the calcium phosphate deposit do not obstruct controlled release of the drug.
Materials Today Communications, 2019
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Designed Monomers and Polymers, 2013
The aim of this study is the synthesis of pH-responsive cationic silica nanoparticles (NPs) by pyridinium-based ionic liquid for the improved sustained release formulations of methotrexate (MTX) as an anionic anticancer drug. Fanctionalized cationic silica NPs were successfully prepared via graft copolymerization of methacrylic acid (MAA) onto vinyl-bond-modified silica NPs. The prepared NPs were characterized using the scanning electron microscopy (SEM), the infrared spectroscopy (IR), and the thermogravimetric analysis. The resultant NPs were uniform spherical NPs with a mean diameter of approximately 160 ± 20 nm. We explored the ionic interaction of MTX NPs in order to generate pH-responsive controlled release system. The cumulative release of MTX-loaded composite microspheres shows a highly desirable precise pH-responsive drug release performance, i.e. loaded drug would not leak in physiological pH (7.4), but would release in a sustained way, where the pH value is lower (4). The protonation of carboxyl groups at mildly acidic condition resulted in a faster dissociation of copolymer/MTX complex, leading to an accelerated release of MTX at pH 4. Thus, complexation of MTX with NPs yielded a drug delivery system affording a pH-triggered release of MTX in an acidic environment. The in vitro cytotoxicity test by MTT assay against breast cancer cells, MCF7 indicates that NPs are nontoxic and suitable to use as drug carriers. Antitumor activity of the MTX-loaded nanocomposites against the cells was kept over the whole experiment process. The results showed that the MTX could be released from the nanocomposites without losing cytotoxicity.
Functionalized Mesoporous Silica as Doxorubicin Carriers and Cytotoxicity Boosters
Nanomaterials
Mesoporous silica nanoparticles (MSNs) bearing methyl, thiol or glucose groups were synthesized, and their encapsulation and release behaviors for the anticancer drug Doxorubicin (Dox) were investigated in comparison with nonporous homologous materials. The chemical modification of thiol-functional silica with a double bond glucoside was completed for the first time, by green thiol-ene photoaddition. The MSNs were characterized in terms of structure (FT-IR, Raman), morphology (TEM), porosity (nitrogen sorption–desorption) and Zeta potential measurements. The physical interactions responsible for the Dox encapsulation were investigated by analytic methods and MD simulations, and were correlated with the high loading efficiency of MSNs with thiol and glucose groups. High release at pH 5 was observed in most cases, with thiol-MSN exhibiting 98.25% cumulative release in sustained profile. At pH 7.4, the glucose-MSN showed 75.4% cumulative release, while the methyl-MSN exhibited a sustai...