【摘 要】
：
Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocryst
【机 构】
：
College of Pharmaceutical Sciences,Southwest University,Chongqing 400716,China;Department of Industr
论文部分内容阅读
Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels,ranging from cells to tissues and to the whole body.In this study,nanocrystals of tetrakis(4-hydroxyphenyl)ethylene(THPE)with an aggregation-induced emission(AIE)property was used as a model to explore intracel-lular absorption mechanism and dissolution kinetics of nanocrystals.Cellular uptake studies were con-ducted with KB cells and characterized by confocal microscopy,flow cytometry,and quantitative analyses.The results suggested that THPE nanocrystals could be taken up by KB cells directly,as well as in the form of dissolved molecules.The cellular uptake was found to be concentration-and time-dependent.In addition,the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and nanocrystals.Kinetic modeling was conducted to further understand the cellular mecha-nism of THPE nanocrystals based on first-order ordinary differential equations(ODEs).By fitting the ki-netic model against experimental measurements,it was found that the initial nanocrystal concentration had a great influence on the dynamic process of dissolution,cellular uptake,and exocytosis of THPE na-nocrystals.As the nanocrystal concentration increased in the culture media,dissolution of endocytosed nanocrystals became enhanced,subsequently driving the efflux of THPE molecules from cells.
其他文献
Since the commercialization of the first liposomes used for drug delivery,Doxil/Caelyx? and Myocet?,tremendous progress has been made in understanding interactions between nanomedicines and biological systems.Fundamental work at the interface of engineeri
The initiation and development of major inflammatory diseases,i.e.,cancer,vascular inflam-mation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immu-notherapy is exerting a critical role against these diseases,whereas
Heart failure(HF)is a global public health problem with high morbidity and mortality.A large number of studies have shown that HF is caused by severe energy metabolism disorders,which result in an insufficient heart energy supply.This deficiency causes ca
When nanoparticles were introduced into the biological media,the protein corona would be formed,which endowed the nanoparticles with new bio-identities.Thus,controlling protein corona for-mation is critical to in vivo therapeutic effect.Controlling the pa
As one of the most important components of caveolae,caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent
Ten years ago,in 2011,we founded Acta Pharmaceutica Sinica B(APSB) with the goal of creating a global high-level forum centered around drug discovery and pharmaceutical research/application.Our first priority was and will always be to serve our readers an
Current advances of immunotherapy have greatly changed the way of cancer treatment.At the same time,a great number of nanoparticle-based cancer immunotherapies(NBCIs)have also been explored to elicit potent immune responses against tumors.However,few NBCI
CD8+ T lymphocytes are pivotal cells in the host response to antitumor immunity.Tumor-driven microenvironments provide the conditions necessary for regulating infiltrating CD8+ T cells in favor of tumor survival,including weakening CD8+ T cell activation,
The beneficial or deleterious effects of nanomedicines emerge from their complex interac-tions with intracellular pathways and their subcellular fate.Moreover,the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the
The intracellular retention of nanotherapeutics is essential for their therapeutic activity.The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors.However,strategies for the intracellular immobilization of nano