Preparation of Chitosan Nanoparticles through a Readily Solvent-Exchange Process for Efficient and Enhanced Gene Delivery.

In view of the excellent prospects of gene therapy and the potential safety and immunogenicity issues challenged by viral vectors, it is of great significance to develop a nonviral vector with low toxicity and low cost. In this work, we report a chitosan nanoparticle (CSNP) to be used as a gene vector prepared through a facile solvent-exchange strategy. Chitosan is first dissolved in ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIM Ac), and then, the solvent is exchanged with water/phosphate-buffered saline (PBS) to remove ionic liquid, forming a final CSNP dispersion after ultrasonication. The prepared CSNP shows a positive surface charge and can condense green fluorescent protein-encoding plasmid (pGFP) at weight ratios (CSNP/pGFP) of 5/1 or higher. Dynamic light scattering size and ζ-potential characterization and gel retardation results confirm the formation of CSNP/pGFP complexes. Compared with plain pGFP, efficient cellular internalization and significantly enhanced green fluorescent protein (GFP) expression are observed by using CSNP as a plasmid vector. Benefitting from the intrinsic biocompatibility, low cost, low immunogenicity, and abundant sources of chitosan, as well as the facile preparation and the efficient gene transfection capacity of CSNP, it is believed that this CSNP could be used as a nonviral gene vector with great clinical translational potentials.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

Solubilization of chitosan in biologically relevant solvents by a low-temperature solvent-exchange method for developing biocompatible chitosan materials.

Chitosan has great potential for biomedical applications. However, the intractable solubility of chitosan is a major bottleneck hampering its utilization. In this work, we report a low-temperature solvent-exchange method to solubilize chitosan in biologically relevant solvents (bio-solvents) including water, salines, and cell culture media. Chitosan was firstly dissolved in ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate (EMIM Ac). The chitosan/IL solution was then dialyzed against bio-solvents at 4 °C, during which a solvent exchange process took place. At the end of 24 h dialysis, aqueous chitosan pseudosolutions formed. Low temperature is found to be crucial for efficient solubilization of chitosan during the solvent exchange process. Increasing temperature to 50 °C leads to the formation of solid chitosan hydrogel. Chitosan in the water-based pseudosolution presents as positively charged particles. The pseudosolution shows a high positive zeta potential of about +52.6 mV and good colloidal stability. The water-based pseudosolutions with different amounts of chitosan contents exhibit the rheological features of weak liquid gels. By using these pseudosolutions, the fabrication of various chitosan materials is realized readily. Both chitosan pseudosolution and its downstream products are highly biocompatible. In this strategy, using IL as a solvent-medium and processing a low-temperature solvent exchange are the two key parameters to solubilize chitosan.

[Observation of Aerosol Optical Properties and New Particle Formation in the Yangtze River Delta].

In a recent field campaign focused on air quality study, aerosol optical properties, particle number concentration, and PM2.5 components were monitored in Changzhou, Jiangsu Province, from May 27 to June 27, 2019. An array of instruments were deployed that included scanning mobility particle size spectrometer (SMPS), aethalometer (AE33), cavity attenuation phase shift single albedo monitor (CAPS-ALB), monitor for aerosols and gases in ambient air (MARGA) and RT-4 organic carbon/elemental carbon (OC/EC) carbon analyzer to study the ① changes in chemical composition and optical parameters of the new particles generated during the campaign period. ② comparison of the aerosol extinction coefficient recorded by these instruments and measured value in the reconstruction of IMPROVE (interagency monitoring of protected visual environment) and the calculated coefficient using MIE theory model were carried out. During the entire campaign, two new particle generation events were observed and also found that the particle size continued to increase from 4 nm to 64 nm. It was monitored that in the initial stage of new particle generation, sulfate contributed greatly. The measured average aerosol extinction coefficient during the period of particle generation, using these instruments was 95.40 Mm-1, while the average aerosol extinction reconstruction using the IMPROVE model was observed to be 140.20 Mm-1. The theoretical calculations based on Mie theory model yielded an average extinction coefficient of 93.54 Mm-1. It was found that the average aerosol extinction in Changzhou is lower than the average value of the urban aerosol extinction coefficient, which is measured to be 300 Mm-1 in China, during this period. The deployment of multiple instruments in a single campaign is more desirable because the combination of all observations helped in better characterization of the physicochemical properties of ambient aerosols from various aspects, including particle size spectrum and chemical composition.