Mesoporous silica nanoparticles as a drug delivery mechanism.

Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

UV-Triggered Drug Release from Mesoporous Titanium Nanoparticles Loaded with Berberine Hydrochloride: Enhanced Antibacterial Activity.

Mesoporous titanium nanoparticles (MTN) have always been a concern and are considered to have great potential for overcoming antibiotic-resistant bacteria. In our study, MTN modified with functionalized UV-responsive ethylene imine polymer (PEI) was synthesized. The characterization of all products was performed by different analyses, including SEM, TEM, FT-IR, TGA, XRD, XPS, and N2 adsorption-desorption isotherms. The typical antibacterial drug berberine hydrochloride (BH) was encapsulated in MTN-PEI. The process exhibited a high drug loading capacity (22.71 ± 1.12%) and encapsulation rate (46.56 ± 0.52%) due to its high specific surface area of 238.43 m2/g. Moreover, UV-controlled drug release was achieved by utilizing the photocatalytic performance of MTN. The antibacterial effect of BH@MTN-PEI was investigated, which showed that it could be controlled to release BH and achieve a corresponding antibacterial effect by UV illumination for different lengths of time, with bacterial lethality reaching 37.76% after only 8 min of irradiation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles have also been studied. The MIC of BH@MTN-PEI was confirmed as 1 mg/mL against Escherichia coli (E. coli), at which the growth of bacteria was completely inhibited during 24 h and the concentration of 5 mg/mL for BH@MTN-PEI was regarded as MBC against E. coli. Although this proof-of-concept study is far from a real-life application, it provides a possible route to the discovery and application of antimicrobial drugs.

Preparation, Characterization, and Evaluation of Mesoporous Silica Nanoparticles in Enhancing Oral Bioavailability of Poorly Water-Soluble Drugs.

BACKGROUND: Breviscapine (BVP) is one of the extracts of several flavonoids of Erigeron breviscapus, which has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease, and angina pectoris. But BVP has poor solubility. OBJECTIVE: The objective of the study is to develop mesoporous silica nanoparticles (MSNs) that can be loaded with a drug with poor water solubility. The MSNs, which were designed for oral administration, enhanced both the dissolution rate and drug loading capacity. METHODS: The use of MSNs as an oral drug delivery system was investigated by SEM, TEM, BETBJH, XRD, FT-IR, and HPLC. Additionally, we examined the oral bioavailability of BVP loaded onto MSNs and examined the cellular cytotoxicity of MSNs. RESULTS: The results indicate that the oral bioavailability of BVP after loading onto MSNs was greater than that of a marketed product. Furthermore, we studied the mechanism by which MSNs enhance the oral absorption of BVP. CONCLUSION: MSNs have the potential to enhance the oral bioavailability of poorly water-soluble drugs by accelerating the drug dissolution rate.

Delivery of paclitaxel by carboxymethyl chitosan-functionalized dendritic fibrous nano-silica: Fabrication, characterization, controlled release performance and pharmacokinetics.

In this study, carboxymethyl chitosan (CMCS) with excellent biocompatibility was used as the "gatekeeper" to design and fabricate a pH-responsive drug delivery system (CMCS-DFNS) as paclitaxel carriers. Characterization results showed that CMCS-DFNS was successfully prepared and the nanocarriers displayed excellent drug loading efficiency of 19.8 %, and the results of the adsorption mechanism revealed that the adsorption of PTX was consistent with the Freundlich isotherm and pseudo-second-order kinetic model. Furthermore, the pH-responsive controlled release behavior at different pH (pH = 7.4, 6.5, and 5.0) was evaluated, and the results demonstrated that the cumulative release at pH 5.0 was 58.8 %, which was 2.7 times higher than that at pH 7.4, suggesting that the carrier exhibited a good pH sensitivity. The results of in vitro cellular experiments further indicated that CMCS-DFNS significantly improved the drug uptake efficiency in breast cancer MCF-7 cells. Importantly, the results of in vivo and cellular pharmacokinetic revealed that CMCS-DFNS can improve the circulation time and enhance the relative bioavailability of paclitaxel. Therefore, the fabricated pH-responsive drug delivery system has potential applications in the delivery of anti-tumor drugs, and provides a new delivery pathway for other compounds with low bioavailability.

Advances in the stimuli-responsive mesoporous silica nanoparticles as drug delivery system nanotechnology for controlled release and cancer therapy.

Mesoporous silica nanoparticles (MSN) have attracted widespread attention in the field of drug delivery and biomedicine due to their unique structure and physicochemical properties. However, MSN still have shortcomings, such as premature drug release, poorly controlled release ability and poor targeting. Therefore, in order to reduce the damage of anti-cancer drugs to normal cells, improve their utilization rate and realize their selective release in tumor cells, "gated" stimuli-responsive mesoporous silicon nanomaterials as antitumor drug delivery carriers have attracted widespread interest among researchers. The "gated" stimuli-responsive nanovalves drug delivery system can only be removed under certain specific stimuli, which makes the drug maintain "zero release" before reaching the lesion site and achieve drug accumulation in tumor cells, effectively reducing the toxic and side effects on normal cells or tissues, and greatly exerting the efficacy of anti-cancer drugs. Therefore, the construction of stimuli-responsive nano-drug delivery systems have great application potential and significance in cancer treatment and controlled release of anti-cancer drugs. This review article emphasizes the research progress of the "gated" stimuli-responsive MSN (e.g. pH, redox potential, enzyme, temperature and light) or controlled drug release and cancer treatment since 2019.

Facile Synthesis of Three Types of Mesoporous Silica Microspheres as Drug Delivery Carriers and their Sustained-Release Properties.

BACKGROUND: Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers for drug delivery. MSNs have been widely used in pharmaceutical research as drug carriers because of their large pore volume, high surface area, excellent biocompatibility, nontoxicity, ease to functionalize, and sustained release effects. MSNs have attracted much attention during drug delivery because of their special structure. OBJECTIVE: The present study aimed to synthesize mesoporous silica nanoparticles (MSNs), dendritic mesoporous silica nanoparticles (DMSN), and hollow mesoporous silica nanoparticles (HMSN) through facile methods, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug. METHODS: MSN, DMSN, and HMSN were characterized by SEM, TEM, FT-IR, nitrogen adsorptiondesorption isotherms, XRD, and zeta potential methods. Subsequently, puerarin (PUE) was used as the active ingredient and loaded into the three mesoporous materials, respectively. And, the drug delivery behavior was measured in PBS solution with different pH values. The sustained-release properties of MSN, DMSN, and HMSN loaded with PUE were investigated. Finally, the biocompatibility and stability of MSN, DMSN, and HMSN were studied by MTT assay and hemolysis assay. RESULTS: Our results showed that MSN, DMSN, and HMSN were successfully synthesized and the three types of mesoporous silica nanoparticles had higher drug loading and encapsulation efficiency. According to the first-order release equation curve and Higuchi equation parameters, the results showed that the PUE-loaded MSN, DMSN, and HMSN exhibited sustained-release properties. Finally, MTT and hemolysis methods displayed that MSN, DMSN, and HMSN had good biocompatibility and stability. CONCLUSION: In this study, MSN, DMSN, and HMSN were successfully synthesized, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug, we provided a theoretical and practical basis for the application of PUE.

An eco-friendly extraction and purification method of nuciferine from Folium nelumbinis with p-sulfonatocalix[6]arenes.

INTRODUCTION: Folium nelumbinis is used as vegetable, functional food and herbal medicine in Asia. p-Sulfonatocalix[6]arene (SC6A) is a water-soluble supramolecular macrocycle and has never been applied to the extraction of herbal products. OBJECTIVE: In this study, SC6A-assisted extraction of nuciferine from Folium nelumbinis has been carried out to develop an eco-friendly extraction process with high extraction efficacy and easy operation. METHODS: Single-factor experiments were adopted to obtain the optimal conditions for the SC6A-assisted extraction of nuciferine from Folium nelumbinis, and then nuciferine and SC6A were separated easily by one-step alkalization. The host-guest complexes between nuciferine and SC6A were analyzed by competitive fluorescence titration, DSC, FT-IR and 1 H-NMR. RESULTS: The optimal SC6A/Folium nelumbinis/solution ratio for extraction was 0.4:1:20 (g/g/mL), with a granulometric fraction below 180 µm and an extraction time of 1 h with soaking. The purity and recovery of nuciferine extracted with SC6A were increased 29.24 and 35.73 times compared with extraction with aqueous solution, respectively. Moreover, a good reusability of SC6A in the extraction of nuciferine was demonstrated. Competitive fluorescence titration, DSC, FT-IR and 1 H-NMR characterization indicated that SC6A could form host-guest complexes with nuciferine at a ratio of 1:1. CONCLUSION: The study provided an eco-friendly, safe and effective nuciferine extraction method, which can be used for the development of nutrition supplements containing nuciferine.

Sugar and pH dual-responsive snap-top nanocarriers based on mesoporous silica-coated Fe3O4 magnetic nanoparticles for cargo delivery.

A facile strategy to prepare snap-top magnetic nanocarriers has been developed where ultrasmall superparamagnetic Fe3O4 nanoparticles were used as the core with mesoporous silica as the shell followed by the covalent installation of a layer of ß-cyclodextrins on the outer surfaces. The smart hybrid nanomaterials showed remarkable pH- and sugar-responsive cargo release property and low cytotoxicity as proved by an MTT assay with HEK293T cell lines.

Supramolecular assembly-induced yellow emission of 9,10-distyrylanthracene bridged bis(pillar[5]arene)s.

9,10-Distyrylanthracene has been introduced to bridge two pillarenes to form a dimeric host, which can assemble into a linear supramolecular polymer upon cooperatively binding to a neutral guest linker, exhibiting yellow fluorescence emission in solution and solid states.

Acetylcholine-triggered cargo release from supramolecular nanovalves based on different macrocyclic receptors.

Acetylcholine (ACh), a neurotransmitter located in cholinergic synapses, can trigger cargo release from mesoporous silica nanoparticles equipped with calixarene- or pillarene-based nanovalves by removing macrocycles from the stalk components. The amount and speed of cargo release can be controlled by varying the concentration of ACh in solution or changing the type of gating macrocycle. Although this proof-of-concept study is far from a real-life application, it provides a possible route to treat diseases related to the central nervous system.

Paraquat detoxification with p-sulfonatocalix-[4]arene by a pharmacokinetic study.

The p-sulfonatocalix[n]arenes are supposed to show potential application in the clinical treatment of viologen poisoning. In the present study, p-sulfonatocalix[4]arene (C4AS), the most common derivative of p-sulfonatocalix[n]arenes, is used to study the antidotic mechanism for paraquat (PQ) by pharmacokinetics in vivo. A high-performance liquid chromatography (HPLC) method was established to determine the concentration of PQ in rat plasma. The results showed that the peak plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-t)) were significantly lower after C4AS intervention than in the PQ intoxication group. It was considered that C4AS has great effective detoxication to PQ poisoning, and the results of in vitro intestinal absorption studies showed that C4AS can inhibit the absorption of PQ via oral administration by forming a stable inclusion constant.

Glucosamine hydrochloride functionalized tetraphenylethylene: a novel fluorescent probe for alkaline phosphatase based on the aggregation-induced emission.

Grafting of glucosamine hydrochloride moieties to tetraphenylethylene (TPE) motif furnished a novel cationic water-soluble tetraphenylethylene derivative (GH-TPE). With aggregation-induced emission properties, GH-TPE was used for fluorometric detection to alkaline phosphatase through enzyme-triggered de-aggregation of the ensemble of GH-TPE and substrate.