ABSTRACT
Traditional Chinese medicine (TCM) formula is one of the unique cultural treasures of Chinese. However, only a few studies have been carried out to deliver TCM formula with utilization of nanocarriers. The purpose of this study was to prepare the hydroxypropyl-β-cyclodextrin complex-over-a-poly(lactic-co-glycolic acid) nanoparticle (HP-β-CD-PLGA NP) for co-delivery and sequential release of five main effective ingredients of Danshen and Sanqi to a specific target, which can provide strategies for design of intelligent drug delivery system of TCM formula. PLGA can be employed as scaffolds for sustained release of both hydrophobic and hydrophilic drugs. HP-β-CD could encapsulate the hydrophobic drugs by forming inclusion complexes. Superparamagnetic iron oxide nanoparticles (SPION) embedded inside PLGA nanoparticles that allow a spatio-specific targeting. HP-β-CD inclusion complex was prepared by an unsaturated alcohol solution method. PLGA NP loaded with SPION was obtained through double emulsion-organic solvents evaporation. Then core-shell PLGA nanosystem was formed by co-incubation of the above two materials. The nanoparticulate system was characterized by confocal laser scanning microscopy (CLSM), laser particle size instrument and transmission electron microscope. Magnetic property was determined by magnet adsorption and vibrating sample magnetometer (VSM). Targeted distribution was investigated by cell uptake and sequential release of multiple components was observed by intracellular distribution of fluorescent probes. Release difference of five components between core and shell of HP-β-CD-PLGA NP was measured by high performance liquid chromatography. The results demonstrated that NP had a unique core-shell structure and possessed superpara-magnetism. Magnetic NP could be ingested site-specifically by L929 cells with the aid of magnetic field, and coumarin-6 and rhodamine B were released from NP sequentially in the L929 cells. In vitro release of multiple components of Danshen and Sanqi from NP exhibited double phase time-controlled release kinetics of quick-release shell and sustained-release core. Therefore, the spatio-temporal nanoplatform has a great capacity for unlocking the full therapeutic potential of displaying synergistic efficacy of TCM formula in the formulation design.
ABSTRACT
Microfluidics is a technology that involves the use of micro-nanoscale pipelines to manipulate fluid mixing. Precise control of the mixing process of laminar flows or liquid droplets by using microfluidics will contribute to the preparation of nanoparticles, which are difficult to be achieved by the conventional methods. Based on the progress in delivery systems of nanoparticulate drug, we provide a summary to introduce the applications of microfluidics in construction of nanoparticulate drug delivery system such as liposomes, polymer nanoparticles and hybrid nanoparticles, and analyze the assembling mechanisms of different nanostructures by using microfluidic precise control. This review will provide a reference in utilization of microfluidic technology more scientifically and reasonably.