A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology
In this study, microfluidic techniques were employed to fabricate liposomes and lipodisks formulations allowing for a reproducible strategy for formulation development. Both liposome and lipodisk of curcumin demonstrated enhancedin vivo performance compared with a conventional formulation in the rat pharmacokinetic study. This combination of approaches with multiple model compounds and lipid-based drug delivery systems provides a systematic guidance to effective strategies to generate higher EE with minimal drug waste and expedite the process for preclinical development when applied to industry compounds. (Source: The AAPS Journal)
Source: The AAPS Journal - October 14, 2021 Category: Drugs & Pharmacology Source Type: research
Cluster Gauss –Newton and CellNOpt Parameter Estimation in a Small Protein Signaling Network of Vorinostat and Bortezomib Pharmacodynamics
Abstract.Ordinary differential equation (ODE) –based models of signal transduction pathways often contain parameters that are unidentifiable or unmeasurable by experimental data, and calibrating such models to data remains challenging. Here, two efficient parameter estimation methods, cluster Gauss–Newton (CGN) and CellNOpt (CNO), were appl ied to fit a signaling network model of U266 multiple myeloma cells to the activity dynamics of key proteins in response to vorinostat and/or bortezomib. A logic-based network model was constructed and transformed to 17 ODEs with 79 parameters estimated within broad ranges of biolog...
Source: The AAPS Journal - October 7, 2021 Category: Drugs & Pharmacology Source Type: research
Bioanalytical Challenges due to Prior Checkpoint Inhibitor Exposure: Interference and Mitigation in Drug Concentration and Immunogenicity Assays
AbstractMonoclonal antibodies (mAbs) are a leading class of biotherapeutics. In oncology, patients often fail on early lines of biologic therapy to a specific target. Some patients may then enroll in a new clinical trial with a mAb specific for the same target. Therefore, immunoassays designed to quantify the current mAb therapy or assess immunogenicity to the drug may be susceptible to cross-reactivity or interference with residual prior biologics. The impact of two approved anti-PD-1 mAbs, pembrolizumab and nivolumab, was tested in several immunoassays for cemiplimab, another approved anti-PD-1 mAb. The methods included ...
Source: The AAPS Journal - October 4, 2021 Category: Drugs & Pharmacology Source Type: research
Considerations for Updates to ICH Q1 and Q5C Stability Guidelines: Embracing Current Technology and Risk Assessment Strategies
Discussion Group (QDG) recommended revision to the ICH series of stability guidelines, the IQ Consortium (International Consortium for Innovation and Quality in Pharmaceutical Development) Science- and Risk-based Stability Working Group conducted a comprehensive review of ICH Q1A, Q1B, Q1C, Q1D, Q1E, and Q5C to identify areas where the guidelines could be clarified, updated, and amended to reflect the potential knowledge gained from current risk-based predictive stability tools and to consider other science- and risk-based stability strategies in accordance with ICH Q8 –12. The recommendations propose a holistic approach...
Source: The AAPS Journal - September 16, 2021 Category: Drugs & Pharmacology Source Type: research
Evaluation of the Humoral Response to Adeno-Associated Virus-Based Gene Therapy Modalities Using Total Antibody Assays
AbstractThe number of viral vector-based gene therapies (GTx) continues to grow with two products (Zolgensma ® and Luxturna®) approved in the USA as of March 2021. To date, the most commonly used vectors are adeno-associated virus-based (AAV). The pre-existing humoral immunity against AAV (anti-AAV antibodies) has been well described and is expected as a consequence of prior AAV exposure. Anti-AAV antibo dies may present an immune barrier to successful AAV transduction and hence negatively impact clinical efficacy and may also result in adverse events (AEs) due to the formation of large immune complexes. Patients may be ...
Source: The AAPS Journal - September 16, 2021 Category: Drugs & Pharmacology Source Type: research
