Read recently published AAPS Journal articles.
The AAPS Journal recently completed a theme showcasing research by emerging scientists: Pioneering Pharmaceutical Science by Emerging Investigators. Only independent investigators who completed their training (including postdoctoral experience) after January 1, 2010, were eligible for the 2018 edition of this theme. There were 32 submissions, and 4 manuscripts were selected for publication. Read the full text online as an AAPS member benefit.
The Phenotypic Effects of Exosomes Secreted from Distinct Cellular Sources: a Comparative Study Based on miRNA Composition
Corresponding Author: Juliane Nguyen, University at Buffalo, The State University of New York, USA
Exosomes are nano-sized vesicles composed of lipids, proteins, and nucleic acids. Their molecular landscape is diverse, and exosomes derived from different cell types have distinct biological activities. Since exosomes are now being utilized as delivery vehicles for exogenous therapeutic cargoes, their intrinsic properties and biological effects must be understood. We performed miRNA profiling and found substantial differences in the miRNA landscape of prostate cancer (PC3) and human embryonic kidney (HEK) 293 exosomes with little correlation in abundance of common miRNAs (R2 = 0.16).
Population pharmacokinetics of AL-335 and its two main metabolites (ALS-022399, ALS-022227) in monotherapy and in combination with Odalasvir and/or Simeprevir
Corresponding Author: Oliver Ackaert, Janssen Research and Development, Global Clinical Pharmacology, Belgium
The aim of the current study was to characterize the time course of plasma concentrations of AL-335 and its main metabolites (ALS-022399 and ALS-022227) after oral administration in healthy and hepatitis C virus (HCV)-infected subjects, in monotherapy as well as in combination with simeprevir and/or odalasvir. Internal evaluation confirmed that the population pharmacokinetic model developed was deemed appropriate to describe the time course of AL-335, ALS-022399, and ALS-022227 plasma concentrations and their associated variability in both healthy and HCV-infected subjects, as well as the interaction effect of simeprevir and/or odalasvir over AL-335 and its metabolites in healthy subjects. This model can be used as a starting point to evaluate drug-drug interaction processes in HCV-infected patients and support the development of a direct-acting antiviral (DAA) combination.
PBPK and its Virtual Populations: the Impact of Physiology on Pediatric Pharmacokinetic Predictions of Tramadol
Corresponding Author: Huybrecht T’jollyn, A Division of Janssen Pharmaceutica NV, Quantitative Sciences, Janssen Research and Development, Belgium
In pediatric PBPK models, age-related changes in the body are known to occur. Given the sparsity of and the variability associated with relevant physiological parameters, different PBPK software providers may vary in their system’s data. In this work, three commercially available PBPK software packages (PK-Sim®, Simcyp®, and Gastroplus®) were investigated regarding their differences in system-related information, possibly affecting clearance prediction.
Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity
Corresponding Author: Brett Ulery, University of Missouri, USA
Through the co-delivery of a model antigenic epitope (Ovalbumin319–340—OVABT) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine—Pam2C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications.
Excerpts are taken from published article abstracts.
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