Nanoparticle-assisted drug delivery has been emerging as an active research area in recent years. The in vivo biodistribution of nanoparticle and its following mechanisms of biodegradation and/or excretion determine the feasibility and applicability of such a nano-delivery platform in the practical clinical translation. In this work we report the synthesis of the highly positive charge, near-infrared fluorescent mesoporous silica nanoparticles (MSNs) that demonstrate rapid hepatobiliary excretion, for use as traceable drug delivery platforms of high capacity. MSNs were incorporated with near-infrared fluorescent dye indocyanine green (ICG) via covalent or ionic bonding, to derive comparable constructs of significantly different net surface charge. In vivo fluorescence imaging and subsequent inductively coupled plasma-mass spectroscopy of harvested tissues, urine, and feces revealed markedly different uptake and elimination behaviors between the two conjugations; with more highly charged moieties (+34.4 mV at pH 7.4) being quickly excreted from the liver into the gastrointestinal tract, while less charged moieties (-17.6 mV at pH 7.4) remained sequestered within the liver. Taken together, these findings suggest that charge-dependent adsorption of serum proteins greatly facilitates the hepatobiliary excretion of silica nanoparticles, and that nanoparticle residence time in vivo can be regulated by manipulation of surface charge.
Cut here to cure: Doxorubicin attached to pH‐sensitive mesoporous silica nanoparticles (MSN‐hydrazone‐Dox) shows potential in the chemotherapeutic treatment of liver cancer. Hydrolysis of the pH‐sensitive hydrazone bond in the acidic environment of endosomes/lysosomes (see picture) releases Dox intracellularly from the MSN nanochannels, resulting in highly efficient apoptotic cell death.
During the past few decades, supercritical fluid (SCF) has emerged as an effective alternative for many traditional pharmaceutical manufacturing processes. Operating active pharmaceutical ingredients (APIs) alone or in combination with various biodegradable polymeric carriers in high-pressure conditions provides enhanced features with respect to their physical properties such as bioavailability enhancement, is of relevance to the application of SCF in the pharmaceutical industry. Herein, recent advances in drug delivery systems manufactured using the SCF technology are reviewed. We provide a brief description of the history, principle, and various preparation methods involved in the SCF technology. Next, we aim to give a brief overview, which provides an emphasis and discussion of recent reports using supercritical carbon dioxide (SC-CO2) for fabrication of polymeric carriers, for applications in areas related to drug delivery, tissue engineering, bio-imaging, and other biomedical applications. We finally summarize with perspectives.
The characterization of near‐infrared (NIR) mesoporous silica nanoparticles (MSN) suitable for in vivo optical imaging with high efficiency is presented. Trimethylammonium groups modified MSN (MSN‐TA) with the average size of 50–100 nm was synthesized with incorporation of the TA groups into the framework of MSN. It was further adsorbed with indocyanine green (ICG) by electrostatic attraction to render MSN‐TA‐ICG as an efficient NIR contrast agent for in vivo optical imaging. The studies in stability of MSN‐TA‐ICG against pH indicated the bonding is stable over the range from acidic to physiological pH. The in vivo biodistribution of MSN‐TA‐ICG in anesthetized rat demonstrated a rather strong and stable fluorescence of MSN‐TA‐ICG that prominent in the organ of liver. Transmission electron microscopy (TEM) imaging and elemental analysis of silicon further manifested the physical and quantitative residences of MSN‐TA‐ICG in major organs. This is the first report of MSN functionalized with NIR‐ICG capable of optical imaging in vivo.
Recently, multidrug
resistance (MDR) has become a major clinical
chemotherapeutic burden that robustly diminishes the intracellular
drug levels through various mechanisms. To overcome the doxorubicin
(Dox) resistance in tumor cells, we designed a hierarchical nanohybrid
system possessing copper-substituted mesoporous silica nanoparticles
(Cu-MSNs). Further, Dox was conjugated to copper metal in the Cu-MSNs
framework through a pH-sensitive coordination link, which is acutely
sensitive to the tumor acidic environment (pH 5.0–6.0). In
the end, the nanocarrier was coated with D-α-Tocopherol polyethylene
glycol 1000 succinate (TPGS), a P-gp inhibitor-entrenched compact
liposome net for obstructing the drug efflux pump. Copper ions in
the framework synergize the antitumor activity of Dox by enhancing
the intracellular reactive oxygen species (ROS) levels through a Fenton-like
reaction-mediated conversion of hydrogen peroxide. Furthermore, intracellularly
generated ROS triggered the apoptosis by reducing the cellular as
well as mitochondrial membrane integrity in MDR cells, which was confirmed
by the mitochondrial membrane potential (MMP) measurement. The advancement
of the design and critical improvement of cytotoxic properties through
free radical attack demonstrate that the proposed hierarchical design
can devastate the MDR for efficient cancer treatment.
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