Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model

Clemens, Daniel L.; Lee, Bai‐Yu; Plamthottam, Sheba; Tullius, Michael V.; Wang, Ruining; Yu, Chia‐Jung; Li, Zilu; Dillon, Barbara Jane; Zink, Jeffrey I.; Horwitz, Marcus A.

doi:10.1021/acsinfecdis.8b00268

Cited by 13 publications

(9 citation statements)

References 39 publications

(64 reference statements)

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“…The injections were performed subcutaneously in the left side of the mice. [ 67 ] After 2 or 3 weeks of treatment, mice were euthanized by exposing them to 5% isoflurane in oxygen, and both femurs and tibiae were removed.…”

Section: Methodsmentioning

confidence: 99%

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

et al. 2021

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Nanotechnology changed the concept of treatment for a variety of diseases, producing a huge impact regarding drug and gene delivery. Among the different targeted diseases, osteoporosis has devastating clinical and economic consequences. Since current osteoporosis treatments present several side effects, new treatment approaches are needed. Recently, the application of small interfering RNA (siRNA) has become a promising alternative. Wnt/β‐catenin signaling pathway controls bone development and formation. This pathway is negatively regulated by sclerostin, which knock‐down through siRNA application would potentially promote bone formation. However, the major bottleneck for siRNA‐based treatments is the necessity of a delivery vector, bringing nanotechnology as a potential solution. Among the available nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of siRNAs. The mesoporous structure of MSNs permits the delivery of siRNAs together with another biomolecule, achieving a combination therapy. Here, the effectiveness of a new potential osteoporosis treatment based on MSNs is evaluated. The proposed system is effective in delivering SOST siRNA and osteostatin through systemic injection to bone tissue. The nanoparticle administration produced an increase expression of osteogenic related genes improving the bone microarchitecture. The treated osteoporotic mice recovered values of a healthy situation approaching to osteoporosis remission.

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Section: Methodsmentioning

confidence: 99%

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

et al. 2021

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“…Moreover, DLS works only on optically clear particle suspension based on the known or well characterized kinematic viscosity of the solvent. In few MSNs studies, hydrodynamic diameters of the nanoparticles were determined by DLS to show both frequency distribution and cumulative particle-size distribution [ 228 ] and mean hydrodynamic diameter [ 246 ]. DLS together with static light scattering (SLS) has been applied to characterize size, stability, and porosity of porous silicon and silica nanoparticles [ 247 ].…”

Section: Analytical Techniquesmentioning

confidence: 99%

“…The surface charge measurements are determined by identifying which electrode the particles are moving towards during electrophoresis [ 249 ]. The method is widely used in the preparation of MSNs to ensure stability, the success of modification, and lack of aggregation [ 228 , 246 , 250 ].…”

Section: Analytical Techniquesmentioning

confidence: 99%

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

et al. 2021

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Conventional administration of drugs is limited by poor water solubility, low permeability, and mediocre targeting. Safe and effective delivery of drugs and therapeutic agents remains a challenge, especially for complex therapies, such as cancer treatment, pain management, heart failure medication, among several others. Thus, delivery systems designed to improve the pharmacokinetics of loaded molecules, and allowing controlled release and target specific delivery, have received considerable attention in recent years. The last two decades have seen a growing interest among scientists and the pharmaceutical industry in mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS). This interest is due to the unique physicochemical properties, including high loading capacity, excellent biocompatibility, and easy functionalization. In this review, we discuss the current state of the art related to the preparation of drug-loaded MSNs and their analysis, focusing on the newest advancements, and highlighting the advantages and disadvantages of different methods. Finally, we provide a concise outlook for the remaining challenges in the field.

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“…The route of administration is important. We emphasized intravenous administration, but for treatment of intracellular pathogens, we found that intramuscular injection was extremely beneficial because of superior pharmacokinetics . Preliminary studies show inhalation administration to be extremely promising for treatment of lung infections.…”

Section: Future Perspectivesmentioning

confidence: 99%

Nanomachines and Other Caps on Mesoporous Silica Nanoparticles for Drug Delivery

et al. 2019

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CONSPECTUS: Mesoporous silica nanoparticles (MSNs) are delivery vehicles that can carry cargo molecules and release them on command. The particles used in the applications reported in this Account are around 100 nm in diameter (about the size of a virus) and contain 2.5 nm tubular pores with a total volume of about 1 cm 3 / g. For the biomedical applications discussed here, the cargo is trapped in the pores until the particles are stimulated to release it. The challenges are to get the particles to the site of a disease and then to deliver the cargo on command. We describe methods to do both, and we illustrate the applicability of the particles to cure cancer and intracellular infectious disease. Our first steps were to design multifunctional nanoparticles with properties that allow them to carry and deliver hydrophobic drugs. Many important pharmaceuticals are hydrophobic and cannot reach the diseased sites by themselves. We describe how we modified MSNs to make them dispersible, imagable, and targetable and discuss in vitro studies. We then present examples of surface modifications that allow them to deliver large molecules such as siRNA. In vivo studies of siRNA delivery to treat triplenegative breast and ovarian cancers are presented. The next steps are to attach nanomachines and other types of caps that trap drug molecules but release them when stimulated. We describe nanomachines that respond autonomously (without human intervention) to stimuli specific to disease sites. A versatile type of machine is a nanovalve that is closed at neutral (blood) pH but opens upon acidification that occurs in endolysosomes of cancer cells. Another type of machine, a snap-top cap, is stimulated by reducing agents such as glutathione in the cytosol of cells. Both of these platforms were studied in vitro to deliver antibiotics to infected macrophages and in vivo to cure and kill the intracellular bacteria M. tuberculosis and F. tularensis. The latter is a tier 1 select agent of bioterrorism. Finally, we describe nanomachines for drug delivery that are controlled by externally administered light and magnetic fields. A futuristic dream for nanotherapy is the ability to control a nano-object everywhere in the body. Magnetic fields penetrate completely and have spatial selectivity governed by the size of the field-producing coil. We describe how to control nanovalves with alternating magnetic fields (AMFs) and superparamagnetic cores inside the MSNs. The AMF heats the cores, and temperature-sensitive caps release the cargo. In vitro studies demonstrate dose control of the therapeutic to cause apoptosis without overheating the cells. Nanocarriers have great promise for therapeutic applications, and MSNs that can carry drugs to the site of a disease to produce a high local concentration without premature release and off-target damage may have the capability of realizing this goal.

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Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse Model

Cited by 13 publications

References 39 publications

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

Nanomachines and Other Caps on Mesoporous Silica Nanoparticles for Drug Delivery

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