Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles

Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(l-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight on cellular behaviors such as uptake. Here we discuss the synthesis of PLGA NPs with varying NP weights and their colloidal and biological properties. Following nanoprecipitation, we have synthesized PLGA NP sizes ranging from 60 to 100 nm by varying the initial PLGA feed in the system. These NPs were found to be stable for a prolonged period in colloidal conditions. We further studied cellular uptake and found that these NPs are cytocompatible; however, they are differentially uptaken by cancer and immune cells, which are greatly influenced by NPs’ weight. The drug delivery potential of these nanoparticles (NPs) was assessed using doxorubicin (DOX) as a model drug, loaded into the NP core at a concentration of 7.0 ± 0.5 wt % to study its therapeutic effects. The results showed that both concentration and treatment time are crucial factors for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting a higher potency at lower concentrations. The observations revealed that DOX-NPs exhibited a higher cellular uptake of DOX compared to the free-DOX treatment group. This will allow us to reduce the recommended dose to achieve the desired effect, which otherwise required a large dose when treated with free DOX. Considering the significance of PLGA-based nanoparticle drug delivery systems, we anticipate that this study will contribute to the establishment of design considerations and guidelines for the therapeutic applications of nanoparticles

GreenHouse gas Observations of the Stratosphere and Troposphere (GHOST): an airborne shortwave-infrared spectrometer for remote sensing of greenhouse gases

GHOST is a novel, compact shortwave-infrared grating spectrometer, designed for remote sensing of tropospheric columns of greenhouse gases (GHGs) from an airborne platform. It observes solar radiation at medium to high spectral resolution (better than 0.3nm), which has been reflected by the Earth's surface using similar methods to those used by polar-orbiting satellites such as the JAXA GOSAT mission, NASA's OCO-2, and the Copernicus Sentinel-5 Precursor. By using an original design comprising optical fibre inputs along with a single diffraction grating and detector array, GHOST is able to observe CO2 absorption bands centred around 1.61 and 2.06µm (the same wavelength regions used by OCO-2 and GOSAT) whilst simultaneously measuring CH4 absorption at 1.65µm (also observed by GOSAT) and CH4 and CO at 2.30µm (observed by Sentinel-5P). With emissions expected to become more concentrated towards city sources as the global population residing in urban areas increases, there emerges a clear requirement to bridge the spatial scale gap between small-scale urban emission sources and global-scale GHG variations. In addition to the benefits achieved in spatial coverage through being able to remotely sense GHG tropospheric columns from an aircraft, the overlapping spectral ranges and comparable spectral resolutions mean that GHOST has unique potential for providing validation opportunities for these platforms, particularly over the ocean, where ground-based validation measurements are not available. In this paper we provide an overview of the GHOST instrument, calibration, and data processing, demonstrating the instrument's performance and suitability for GHG remote sensing. We also report on the first GHG observations made by GHOST during its maiden science flights on board the NASA Global Hawk unmanned aerial vehicle, which took place over the eastern Pacific Ocean in March 2015 as part of the CAST/ATTREX joint Global Hawk flight campaign