Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane

Poly-(γ-l-glutamylglutamine)–paclitaxel (PGG–PTX) is a novel polymer-based formulation of paclitaxel (PTX) in which the PTX is linked to the polymer via ester bonds. PGG–PTX is of interest because it spontaneously forms very small nanoparticles in plasma. In mouse models, PGG–PTX increased tumor exposure to PTX by 7.7-fold relative to that produced by PTX formulated in Cremophor. In this study, the efficacy of PGG–PTX was compared to that of Abraxane, an established nanoparticular formulation of PTX, in three different tumor models. Efficacy was quantified by delay in tumor growth of NCI H460 human lung cancer, 2008 human ovarian cancer and B16 melanoma xenografts growing in athymic mice following administration of equitoxic doses of PGG–PTX and Abraxane administered on either a single dose or every 7 day schedule. Toxicity was assessed by change in total body weight. The efficacy and toxicity of PGG–PTX was shown to increase with dose in the H460 model. PGG–PTX was ~1.5-fold less potent than Abraxane. PGG–PTX produced statistically significantly greater inhibition of tumor growth than Abraxane in all three tumor models when mice were given single equitoxic doses of drug. When given every 7 days for 3 doses, PGG–PTX produced greater inhibition of tumor growth while generating much less weight loss in mice bearing H460 tumors. PGG–PTX has activity that is superior to that of Abraxane in multiple tumor models. PGG–PTX has the potential to out-perform Abraxane in enhancing the delivery of PTX tumors while at the same time further reducing the toxicity of both single dose and weekly treatment regimens

Pharmacokinetics and tissue distribution of PGG–paclitaxel, a novel macromolecular formulation of paclitaxel, in nu/nu mice bearing NCI-460 lung cancer xenografts

PGG–PTX is a water-soluble formulation of paclitaxel (PTX), made by conjugating PTX to poly(l-γ-glutamylglutamine) acid (PGG) via ester bonds, that spontaneously forms a nanoparticle in aqueous environments. The purpose of this study was to compare the pharmacokinetics and tissue distribution of PTX following injection of either free PTX or PGG–PTX in mice. Both [3H]PTX and PGG–[3H]PTX were administered as an IV bolus injection to mice bearing SC NCI-H460 lung cancer xenografts at a dose of 40-mg PTX equivalents/kg. Plasma, tumor, major organs, urine, and feces were collected at intervals out to 340 h. Total taxanes, taxane extractable into ethyl acetate, and native PTX were quantified by liquid scintillation counting and HPLC. Conjugation of PTX to the PGG polymer increased plasma and tumor C max, prolonged plasma half-life and the period of accumulation in tumor, and reduced washout from tumor. In plasma injection of PGG–PTX increased total taxane AUC0–340 by 23-fold above that attained with PTX. In tumors, it increased the total taxane by a factor of 7.7, extractable taxane by 5.7, and native PTX by a factor of 3.5-fold. Conjugation delayed and reduced total urinary and fecal excretion of total taxanes. Incorporation of PTX into the PGG–PTX polymer significantly prolonged the half-life of total taxanes, extractable taxane, and native PTX in both the plasma and tumor compartments. This resulted in a large increase in the amount of active PTX delivered to the tumor. PGG–PTX is an attractive candidate for further development

Appearance Modeling of Living Human Tissues

This is the peer reviewed version of the following article: Nunes, A.L.P., Maciel, A., Meyer, G.W., John, N.W., Baranoski, G.V.G., & Walter, M. (2019). Appearance Modeling of Living Human Tissues, Computer Graphics Forum, which has been published in final form at https://doi.org/10.1111/cgf.13604. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingThe visual fidelity of realistic renderings in Computer Graphics depends fundamentally upon how we model the appearance of objects resulting from the interaction between light and matter reaching the eye. In this paper, we survey the research addressing appearance modeling of living human tissue. Among the many classes of natural materials already researched in Computer Graphics, living human tissues such as blood and skin have recently seen an increase in attention from graphics research. There is already an incipient but substantial body of literature on this topic, but we also lack a structured review as presented here. We introduce a classification for the approaches using the four types of human tissues as classifiers. We show a growing trend of solutions that use first principles from Physics and Biology as fundamental knowledge upon which the models are built. The organic quality of visual results provided by these Biophysical approaches is mainly determined by the optical properties of biophysical components interacting with light. Beyond just picture making, these models can be used in predictive simulations, with the potential for impact in many other areas

CLINICAL SIGNIFICANCE OF ENDOTHELIAL DYSFUNCTION IN NON-ST-SEGMENT-ELEVATION ACUTE CORONARY SYNDROME IN SUBJECTS UNDER 55 YEARS OF AGE

The role and clinical significance of endothelial dysfunction (ED) in the diagnostics and prognosis of non-ST-segment-elevation acute coronary syndrome (ACS) in subjects under 55 years of age with verified CHD (by heart catheterization). The comparison group was made of 32 patients with stable angina (SA) II and III functional classes. Non-Q-wave myocardial infarction was diagnosed in 50 (37 %) troponin-positive patients, unstable angina in 84 (63 %) troponin-positive patients. Endothelial function was evaluated by plasma and red blood cells nitrates and I-arginine levels, the number of desquamated endotheliocytes (DE) in plasma, concealed endothelial dysfunction was revealed. A reliable increase of nitrates and DE has been found, most marked in patients with ACS. ED may be present as concealed (compensated), intermediate (subcompensated) and acute (decompensated) forms