Nano- and microparticles have increasingly widespread applications in nanomedicine, ranging from drug delivery to imaging. Poly(lactic-co-glycolic acid) (PLGA) particles are the most widely-applied type of particles due to their biocompatibility and biodegradability. Here, we discuss the preparation of PLGA particles, and various modifications to tailor particles for applications in biological systems. We highlight new preparation approaches, including microfluidics and PRINT method, and modifications of PLGA particles resulting in novel or responsive properties, such as Janus or upconversion particles. Finally, we describe how the preparation methods can- and should-be adapted to tailor the properties of particles for the desired biomedical application. Our aim is to enable researchers who work with PLGA particles to better appreciate the effects of the selected preparation procedure on the final properties of the particles and its biological implications. Nanoparticles are increasingly important in the field of biomedicine. Particles made of polymers are in the spotlight, due to their biodegradability, biocompatibility, versatility. In this review, we aim to discuss the range of formulation techniques, manipulations, and applications of poly(lactic-co-glycolic acid) (PLGA) particles, to enable a researcher to effectively select or design the optimal particles for their application. We describe the various techniques of PLGA particle synthesis and their impact on possible applications. We focus on recent developments in the field of PLGA particles, and new synthesis techniques that have emerged over the past years. Overall, we show how the chemistry of PLGA particles can be adapted to solve pressing biological needs.
We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.
12 February 2008 in Journal of the American Chemical Society
This article describes an in vivo imaging method for visualizing and quantifying a specific cell population. Cells are labeled ex vivo with a perfluoropolyether nanoparticle tracer agent and then detected in vivo using 19F MRI following cell transfer. 19F MRI selectively visualizes only the labeled cells with no background, and a conventional 1H image taken in the same imaging session provides anatomical context. Using the nonobese diabetic mouse, an established model of type 1 diabetes, 19F MRI data were acquired showing the early homing behavior of diabetogenic T cells to the pancreas. A computational algorithm provided T cell counts in the pancreas. Approximately 2% of the transferred cells homed to the pancreas after 48 hr. The technique allows for both unambiguous detection of labeled cells and quantification directly from the in vivo images. The in vivo quantification and cell trafficking patterns were verified using 19F spectroscopy and fluorescence microscopy in excised pancreata. The labeling procedure did not affect T‐cell migration in vivo. This imaging platform is applicable to many cell types and disease models and can potentially be used for monitoring the trafficking of cellular therapeutics. Magn Reson Med 58:725–734, 2007.
Noninvasive methods to image the trafficking of phenotypically defined immune cells are paramount as we attempt to understand adaptive immunity. A 19F MRI‐based methodology for tracking and quantifying cells of a defined phenotype is presented. These methods were applied to a murine inflammation model using antigen‐specific T cells. The T cells that were intracellularly labeled ex vivo with a perfluoropolyether (PFPE) nanoemulsion and cells were transferred to a host receiving a localized inoculation of antigen. Longitudinal 19F MRI over 21 days revealed a dynamic accumulation and clearance of T cells in the lymph node (LN) draining the antigen. The apparent T‐cell numbers were calculated in the LN from the time‐lapse 19F MRI data. The effect of in vivo T‐cell division on the 19F MRI cell quantification accuracy was investigated using fluorescence assays. Overall, in vivo cytometry using PFPE labeling and 19F MRI is broadly applicable to studies of whole‐body cell biodistribution. Magn Reson Med, 2009.