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It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate‐specific membrane antigen (PSMA) targeting agents PSMA‐11 and PSMA‐617, which accumulate in prostate tumours, allow for [68Ga]Ga3+‐radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [68Ga]Ga‐PSMA‐617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [68Ga]Ga‐PSMA‐617‐ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [68Ga]Ga‐PSMA‐617‐ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [68Ga]Ga‐PSMA‐617‐ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68Ga]Ga‐PSMA‐617‐ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild‐type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [68Ga]Ga‐PSMA‐617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine whether shellac, a naturally occurring material with enteric properties, could be processed in supercritical CO 2 (sc-CO 2 ) using the particles from gas saturated solution (PGSS) process and how process parameters affect the physico-chemical properties of shellac. In-situ attenuated total reflection fourier transform infra-red (ATR-FTIR) spectroscopy showed that CO 2 dissolves in shellac with solubility reaching a maximum of 13% (w/w) at 300 bar pressure and 40 °C and maximum swelling of 28%. The solubility of sc-CO 2 in shellac allowed for the formation of porous shellac structures of which the average pore diameter and pore density could be controlled by adjustment of operating pressure and temperature. In addition, it was possible to produce shellac microparticles ranging in average diameter from 180 to 300 μm. It was also shown that processing shellac in sc-CO 2 resulted in accelerated esterification reactions, potentially limiting the extent of post-processing “ageing” and thus greater stability. Due to additional hydrolysis reactions enhanced by the presence of sc-CO 2 , the solubility of shellac at pH 7.5 was increased by between 4 and 7 times, while dissolution rates were also increased. It was also shown that the in-vitro dissolution profiles of shellac could be modified by slight adjustment in operating temperatures. [ABSTRACT FROM AUTHOR]

Purpose: There is significant interest in the application of nanoparticles to deliver immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating polymer) could be conjugated to PLGA and nanoparticles from this copolymer would possess immunostimulatory activity, be non-cytotoxic and function as an effective sustained drug release system., Methods: Carbodiimide chemistry was employed to conjugate curdlan to PLGA. The conjugate (C-PLGA) was characterized using (1)H and (13)C NMR, FTIR, DSC and TGA. Nanoparticles were synthesized using an emulsion-solvent evaporation technique. Immunostimulatory activity was characterized in THP-1 derived macrophages. MTT assay and real-time impedance measurements were used to characterize polymer and nanoparticle toxicity and uptake in macrophages. Drug delivery capability was assessed across Caco-2 cells using rifampicin as a model drug., Results: Spectral characterization confirmed successful synthesis of C-PLGA. C-PLGA nanoparticles enhanced phosphorylated ERK production in macrophages indicating cell stimulation. Nanoparticles provided slow release of rifampicin across Caco-2 cells. Polymers but not nanoparticles altered the adhesion profiles of the macrophages. Impedance measurements suggested Ca(2+) dependent uptake of nanoparticles by the macrophages., Conclusions: PLGA nanoparticles with macrophage stimulating and sustained drug delivery capabilities have been prepared. These nanoparticles can be used to stimulate macrophages and concurrently deliver drug in infectious disease therapy.