Mesoporous Silica Drug Delivery System Research Articles

Rod-shaped hollow mesoporous silica drug delivery system: synthetic design, ibuprofen delivery, and optical imaging

Rod-shaped hollow mesoporous silica drug delivery system: synthetic design, ibuprofen delivery, and optical imaging

Recent Progress in Diatom Biosilica: A Natural Nanoporous Silica Material as Sustained Release Carrier.

A drug delivery system (DDS) is a useful technology that efficiently delivers a target drug to a patient's specific diseased tissue with minimal side effects. DDS is a convergence of several areas of study, comprising pharmacy, medicine, biotechnology, and chemistry fields. In the traditional pharmacological concept, developing drugs for disease treatment has been the primary research field of pharmacology. The significance of DDS in delivering drugs with optimal formulation to target areas to increase bioavailability and minimize side effects has been recently highlighted. In addition, since the burst release found in various DDS platforms can reduce drug delivery efficiency due to unpredictable drug loss, many recent DDS studies have focused on developing carriers with a sustained release. Among various drug carriers, mesoporous silica DDS (MS-DDS) is applied to various drug administration routes, based on its sustained releases, nanosized porous structures, and excellent solubility for poorly soluble drugs. However, the synthesized MS-DDS has caused complications such as toxicity in the body, long-term accumulation, and poor excretion ability owing to acid treatment-centered manufacturing methods. Therefore, biosilica obtained from diatoms, as a natural MS-DDS, has recently emerged as an alternative to synthesized MS-DDS. This natural silica carrier is an optimal DDS platform because culturing diatoms is easy, and the silica can be separated from diatoms using a simple treatment. In this review, we discuss the manufacturing methods and applications to various disease models based on the advantages of biosilica.

The impact of drug-loading factors on the solid-state form of ritonavir-mesoporous silica systems

Among the formulation techniques used to enhance thesolubility and dissolution rate of poorly, aqueous-soluble drugs, mesoporoussilica drug delivery systems have shown promise. A range of processes areemployed to load drugs onto silica and solvent-based approaches are widelyemployed. This study aims to understand the influence of drug concentration insolvent and drug-silica ratio on drug solid-state form and amorphization withinsilica. Ritonavirwhich belongs to  BCS Class II was used asa model drug. Ritonavir wasloaded into Syloid®244FP using a solvent evaporationmethod. Ritonavir loading percentage was calculated based on the assumptionthat the entire specific surface area of silica is exposed and available fordrug adsorption.  Ethanolsolutions with 3 different ritonavir concentrations; 70%, 32% and 20% saturatedsolubility at 25°C were employed. Ritonavir was loaded into silica at 1:1, 1:2and 1:3 ritonavir:silica ratios.  Allsystems included ritonavir loaded beyond monolayer surface coverage. Ritonavir- Syloid®244 FP formulations were characterisedusing DSC, PXRD, FT-IR, and TGA. The results showed that all ritonavir-Syloid®244 FP systemsprepared contained ritonavir in a non-crystalline state.

In vivo study of light-driven naproxen release from gated mesoporous silica drug delivery system

A drug delivery system based on mesoporous particles MCM-41 was post-synthetically modified by photo-sensitive ligand, methyl-(2E)-3-(4-(triethoxysilyl)-propoxyphenyl)-2-propenoate (CA) and the pores of MCM-41 particles were loaded with Naproxen sodium salt (NAP). The CA was used as a photoactive molecule that can undergo a reversible photo-dimerization by [2π + 2π] cycloaddition when irradiated with UV light of specific wavelengths. Thus, it has a function of gate-keeper that is responsible for opening/closing the pores and minimizing premature release of NAP. The physicochemical properties of the prepared system were studied by infrared spectroscopy (IR), nitrogen adsorption measurements, thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDX). The mechanism of the opening/closing pores was confirmed by UV measurements. In vitro and in vivo drug release experiments and the concentration of released NAP was determined by UV spectroscopy and high-performance liquid chromatography (HPLC). In vivo drug release in the blood circulatory system of rats has demonstrated the effective photo-cleavage reaction of CA molecules after UV-light stimulation. The localization and morphological changes of the particles were studied in the blood and liver of rats at different time intervals. The particles in the blood have been shown to retain their original rod-like shape, and the particles in the liver have been hydrolysed, which has resulted in spherical shape with a reduced size.

PH-responsive mesoporous silica drug delivery system, its biocompatibility and co-adsorption/co-release of 5-Fluorouracil and Naproxen

A pH-responsive drug delivery system composed of N-(propyl)aniline (N-ANI) modified mesoporous silica nanoparticles as a carrier, and β-cyclodextrin (β-CD) as a cap was prepared and investigated. The system was studied for co-adsorption and co-delivery of two different drugs; an anticancer drug 5-fluorouracil (5-FU), and anti-inflammatory agent naproxen (NAP). Detailed adsorption study of the drugs themselves as well as in their mutual mixture was performed. The drug release experiments were realized in simulated body fluid (pH = 7.4) and slightly acidic medium (pH = 5) imitating the pH of tumor affected area. The experiments showed, that at physiological pH 7.4, the prepared drug delivery system released no drug, at slightly acidic medium (pH = 5) the β-CD caps were loosened, and drugs were released (88.5% and 98.7% for 5-FU and NAP, respectively). To investigate the efficiency of the designed system for the delivery in biological environment, the biocompatibility and cytotoxicity experiments were performed using U87 MG and SKBR3 cancer cells by fluorescence microscopy, flow-cytometry, MTT. apoptotic and CAM assays.

Dual response to pH and chiral microenvironments for the release of a flurbiprofen-loaded chiral self-assembled mesoporous silica drug delivery system

This study examined the effects of pH and chirality on the release of flurbiprofen (FP)-loaded chiral (L/D) self-assembled mesoporous silica nanoparticles (CSA-L/D-MSNs), which were synthesized using cationic cetyltrimethyl ammonium bromide (CTAB) as a template and chiral modified using L/D-tartaric acids. The morphology and physicochemical properties of the CSA-L/D-MSNs were systemically determined and compared with those of non-functionalized mesoporous silica nanoparticles (MSN). The results showed that the CSA-L/D-MSNs were spherical nanoparticles, and the chirality in the L/D-tartaric acids was successfully imparted to the CSA-L/D-MSNs. FP could be loaded into the CSA-L/D-MSNs and was effectively transformed from the crystalline state to an amorphous state after drug loading due to the finite size effect. The release of FP@CSA-L/D-MSNs was faster than that of FP in a pH 1.2 medium and slower in a pH 6.8 medium, and it was better than that of FP@MSNs in both release mediums. Meanwhile, the FP@CSA-L/D-MSNs exhibited a clearly enhanced pH response because the negatively charged carboxyl groups on their surface induced stronger electrostatic repulsion between FP and CSA-L/D-MSNs. Moreover, the effect of the chiral environment on the release of FP@CSA-L/D-MSNs was further studied by introducing small-molecule chiral additives (L/D-alanine). It was found that the release of FP was inhibited in a chiral environment. Particularly, the CSA-L/D-MSNs began to exert the chiral recognition function, in which the CSA-L-MSN responded to chiral stimuli and enhanced the cumulative release amount from 84.25 %–89.11 % in a pH 6.8-L medium, while the CSA-D-MSN showed a suppressed release in the pH 6.8-L medium. Notably, the CSA-L/D-MSNs exhibited intelligent drug release by both chirality response and pH response, and will provide valuable guidance for the design of drug delivery systems.

Study of pH-Responsive and Polyethylene Glycol-Modified Doxorubicin-Loaded Mesoporous Silica Nanoparticles for Drug Delivery.

Tumor-targeted drug delivery systems represent challenging and widely investigated strategies to enhance cancer chemotherapy. In this study, we introduce a novel high-hydrophilic mesoporous silica nanoparticle system with a pH-sensitive drug release. The resultant composite nanoparticles appear as spheres of uniform size (450±25 nm) with a porous structure, which enables a high drug-loading ratio. Through modification of chitosan and polyethylene glycol monomethyl ether, the modified mesoporous silica was non-toxic to normal cells, but effective at inducing tumor cell death. With regard to the characteristics of drug release, the modified mesoporous silica clearly displayed a pH-stimulated release of the model drug doxorubicin hydrochloride in an acidic phosphate buffer solution (pH 4.0 and 6.0). The release was much greater than that observed in neutral or alkaline phosphate buffer solutions (pH 7.3 and 8.0). Furthermore, the release behavior was in accordance with the Higuchi model, indicating that this modified mesoporous silica drug delivery system can exhibit controlled release. The above results imply that the modified mesoporous silica is an effective drug delivery system for cancer therapy.

Single subconjunctival injection formulation using sol-gel mesoporous silica as a controlled release system for drop-free post-cataract surgery care.

To develop a mesoporous silica drug delivery system and target drop-free care after cataract surgery with a single subconjunctival injection. Laboratory. Experimental animal study. Ketorolac was infiltration-loaded into sol-gel mesoporous silica particles encapsulated with poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) using a layer-by-layer adsorption technique (SG-Ket-LBL). The formulation was subjected to an in vitro and in vivo drug release study in addition to ocular toxicology evaluation. Thermogravimetric analysis revealed that the drug loading efficiency was 4.4% for the SG-Ket-LBL particles. The in vivo safety study demonstrated that the formulation was well tolerated after subconjunctival injection and aqueous humor pharmacokinetics showed sustained therapeutic drug release for the targeted time window of 6 to 8 weeks. Findings indicated that sol-gel mesoporous silica could be used as a drug carrier for subconjunctival administration. The tested formulation, SG-Ket-LBL, provided therapeutic ketorolac for 6 to 8 weeks, which might be used for a single subconjunctival injection to replace nonsteroidal anti-inflammatory drug eyedrops after cataract surgery.

PH-responsive mesoporous silica drug delivery system for targeted cancer chemotherapy

ABSTRACT In this paper, a kind of pH-responsive mesoporous silica targeted drug delivery system (DOX-loaded N-CQDs/HA gated pSiO2/MPEG-Glu) was designed and synthesised. In this system, active mesoporous silica (pSiO2) worked as a carrier material, methoxy polyethene glycol amine (MPEG) and L-glutamic acid (Glu) can be coupled and grafted to the surface of the pSiO2 drug carrier to improve the stability of the drug delivery system, nitrogen-doped carbon quantum dots (N-CQDs) and hyaluronic acid (HA) can inhibit the rapid release of drug. Ultraviolet (UV-Vis) spectrum showed that the drug-loading rate of DOX is 8.9%, the drug release in vitro study suggested that the prepared silica drug delivery system had significant pH-responsive and targeted DOX release, the drug release rate is 55.7% at pH = 5.0, which was much higher than the release of pH = 7.4; CLSM and MTT showed that the drug delivery system can enter into cancer cells through endocytosis and the DOX can act on cell nucleus, exhibiting a targeted therapy on cancer cells.

Near-infrared light triggered drug release from mesoporous silica nanoparticles.

Stimuli triggered drug delivery systems enable controlled release of drugs at the optimal space and time, thus achieving optimal therapeutic effects. As one of the most important stimuli used in bioapplications, near-infrared (NIR) light possesses unique advantages such as deep tissue penetration with minimum auto-fluorescence & tissue scattering and high biosafety. Mesoporous silica nanoparticles (MSNs) are one of the most studied nanocarriers; apart from having a high surface area and large pore volume for loading of drugs, they can be easily functionalized with inorganic nanomaterials and stimuli responsive polymers or organic switch molecules, creating possibilities for designing complex stimuli triggered drug delivery systems. Considering the high tissue penetration depth of NIR light and the unique mesoporous structure of MSNs, NIR responsive inorganic nanoparticle functionalized MSNs can be further combined with stimuli responsive materials to form smart "nano-devices" for controlled drug delivery toward tumors, and to date much progress has been made. In this article, recent advances in the design of NIR triggered mesoporous silica drug delivery systems are systematically summarized and some outstanding studies are highlighted. We will also discuss the shortcomings, challenges and opportunities in the field.

Controlled assemblies of stimuli-responsive mesoporous silica drug delivery systems for controlled release of drugs

There has been an ever increasing interest in developing stimuli-responsive mesoporous silica drug delivery systems to improve therapeutic efficacy and minimize the adverse effects of drugs. This paper reports the works of our research group on valved and gated mesoporous silica drug delivery systems. Biocompatible mesoporous silica nanoparticles (MSNs), as drug carriers, were modified with active group-terminated silanes via self-assembly followed by diverse functionalization, a variety of macrocyclic hosts, proteins, DNA, and quantum dots were bound to the MSN surfaces to develop nanovalves and nanogates, through multiple noncovalent interactions, dynamic covalent bonds, and even strong covalent bonds, for the encapsulation of drugs within MSN pores, thus smart valved and gated MSN drug delivery systems were constructed. Under the stimuli of pH, redox, competitive binding, enzymes, and near infrared lights, controlled release of the encapsulated drugs was realized, because of the destruction of multiple noncovalent interactions, the cleavage of dynamic covalent bonds, and the disassociation of gatekeeping scaffolds. The carboxylate-substituted pillar [6] arene (CPA [6] )-valved dimethylbenzimidazolium or bipyridinium-functionalized MSN drug delivery systems were constructed for acidic pH, competitive binding, and metal chelating-responsive controlled release. The γ -CD-gated MSN delivery system functionalized with disulfide-linked carbamoylphenylboronic acid moieties and amines via dual dynamic covalent bonds with dual drug loading was constructed for simultaneous and cascade release of two drugs. It is a smart strategy to take advantage of the specific structures and properties of cyclodextrins (CDs) for use in the MSN drug delivery systems not only as gatekeepers but also as drug carriers. The γ -CD-gated MSN delivery system provided a smart platform for combination drug therapy, in addition to resistance to serum and normal blood glucose levels. The concanavalin A (Con A)-gated mannose-functionalized MSN drug delivery system via multivalent carbohydrate - protein interactions was constructed for the controlled release of drugs either by acidic pH or by competitive binding of glucose at high concentrations. The long and flexible spacers linked with the mannose ligands played an important role in adjusting the local spatial arrangement of the ligands to favor multivalent protein binding, as did the surface density of the ligands. The MSN drug delivery systems functionalized with N -(3-trimethoxysilylpropyl)ethylenediamine triacetate ligands, in the presence of metal ions with and without myoglobin containing surface-accessible histidine residues, were constructed for pH-responsive controlled release. Both the metal-latching ligands and the metal-chelating proteins played a synergetic role in gating MSNs for high-loading drug delivery and stimuli-responsive controlled release. The DNA-gated MSN drug delivery system functionalized with disulfide-linked acridinamine intercalators was constructed for multi-responsive controlled release under different stimuli, including disulfide reducing agents, elevated temperature, and deoxyribonuclease I. The DNA-gated MSN drug delivery system integrated multiple responses and AND logic gate operations into a single smart nanodevice not only for codelivery of drugs and DNA/genes but also for cascade release of two drugs in combination of dual stimuli. The DNA-gated gold nanorod-embedded MSN delivery system functionalized with titanium(IV)-chelating phosphonates with dual drug loading was constructed for simultaneous and cascade release of two drugs. Coordination chemistry is the first strategy for DNA cappings through multivalent chelating interactions in drug delivery systems not only as gatekeepers but also as drug carriers. The two drugs were simultaneously released upon triggering of endonuclease degradation or photothermal dehybridization and were successively released upon first triggering of basic pH and subsequent triggering of photothermal heating. The combination of NIR light-based thermotherapy and triggered chemotherapy (thermo-chemotherapy) could maximize therapeutic efficacy. In addition, the ZnO quantum dot (QD)-gated hollow mesoporous silica drug delivery system was constructed for pH and redox- responsive controlled release, and the ZnO QD-gated mesoporous carbon nanoparticle (MCN) drug delivery system was for pH-responsive controlled release. These constructed stimuli-responsive MSN drug delivery systems have promising applications in targeted tumor therapy.

Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance.

Multidrug resistance (MDR) is known to be a great obstruction to successful chemotherapy, and considerable efforts have been devoted to reverse MDR including designing various functional drug delivery systems. In this study, hybrid lipid-capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli-responsive drug release to circumvent MDR, were specially designated for drug delivery. After modifying MSNs with hydrophobic chains through disulfide bond on the surface, lipid molecules composing polymer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to self-assemble into a surrounded lipid layer via hydrophobic interaction acting as smart valves to block the pore channels of carrier. The obtained LTMSNs had a narrow size distribution of ca. 190 nm and can be stably dispersed in body fluids, which may ensure a long circulating time and ideal enhanced permeability and retention effect. Doxorubicin (DOX) was chosen as a model drug to be encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous silica drug delivery system can achieve redox and pH-responsive release of DOX, thereby avoiding the premature leakage of drug before reaching the specific site and releasing DOX within the cancerous cells. Owing to the presence of TPGS-containing lipid layer, LTMSNs-DOX exhibited higher uptake efficiency, cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr cells compared with DOX solution, proving to be a promising vehicle to realize intracellular drug release and inhibit drug efflux.

PH- and redox-triggered synergistic controlled release of a ZnO-gated hollow mesoporous silica drug delivery system.

Hollow mesoporous silica spheres (HMSS) have a hierarchical mesoporous structure composed of a hollow cavity and mesoporous shell available for high capacity drug storage. The covalent attachment of ZnO quantum dots (QDs) to the HMSS outer surface as gatekeepers via disulfide-conjugated two amide linkages encapsulated the anticancer drugs doxorubicin (DOX) within the HMSS cavities and pores, and minimized premature release of the drug. The controlled release of the drug from the ZnO-gated HMSS delivery system was realized by the dissolution of ZnO QDs upon a decrease in pH and cleavage of the disulfide bonds, which indicates that the pH- and redox-responsive controlled release of the drugs could be synergically stimulated by tumor cells with weakly acidic environments and high-expressed glutathione. The constructed ZnO-gated HMSS delivery system has promising applications in site-specific drug release for tumor chemotherapy.

Recent Advances of Mesoporous Silica Based Multifunctional Nano Drug Delivery Systems

Mesoporous silica materials have attracted much attention for their potential biomedical applications due to their tailored mesoporous structure, large surface area, good biocompatibility, and the ease of surface functionalization. In the past few years, the mesoporous silica based drug nanocarriers have become the research focus of many researchers. This article reviews the recent research advances of mesoporous silica based multifunctional drug delivery systems with targeting modification and bioimaging, and details the design, surface modification, and applications in drug delivery field of mesoporous silica based drug delivery systems with diverse morphologies(such as hollow/rattle-type, nanotubes, etc.). Finally, we analyze the existing problems in practical applications and outlook the future development trends of mesoporous silica based drug delivery systems(including the specific morphological, multifunctional hybrid, and biodegradable mesoporous silica drug delivery systems).