Strategies to develop highly drug-tolerant cell-based neutralizing antibody assay: neutralizing antidrug antibodies extraction and drug depletion

Aim: Drug interference poses great analytical challenges for cell-based neutralizing antidrug antibodies (NAb) assay. The work aimed to improve assay drug tolerance through biotin-drug extraction with acid dissociation method optimization and developing new approach. Results: The NAb extraction with biotin-drug extraction with acid dissociation approach has been optimized by reducing biotinylated drug leaching and improving NAb elution efficiency, resulting in drug tolerance of up to 160 μg/ml. To circumvent the low acid elution efficiency of NAb from drug, a novel drug depletion approach was developed, which combined acid dissociation and drug targeted crosslinked capture, achieved drug tolerance up to 400 μg/ml. At last, a strategy workflow for sample pretreatment approach selection and optimization was established for improving drug tolerance of NAb assay. Conclusion: We demonstrated that reduced biotinylated drug leaching and the high NAb elution efficiency was critical for improving assay drug tolerance. Drug depletion offers an alternative approach to overcome low NAb elution efficiency.

New Polymer Inclusion Membrane Containing β-Cyclodextrin Polymer: Application for Pharmaceutical Pollutant Removal from Waste Water

We present herein the preparation of novel polymer inclusion membranes (PIMs) containing insoluble β-CD polymer as a carrier, polyvinyl chloride as a base polymer, and dibuthylphtalate (DBP) as a plasticizer in varying proportions. The prepared PIMs can be obtained by a simple, fast, and high-yield preparation process. Physicochemical characterizations of such membranes occurred in a homogeneous structure. In addition, Fourier-transform infrared Spectroscopy (FT-IR) analysis found that DBP was inserted between these polymeric chains by non-covalent interactions. This led to a spacing of PVC/poly(β-cyclodextrin) chains inducing a better access of guest molecules to PIM cyclodextrins. To achieve the elimination of ibuprofen and progesterone, two examples of emerging environmental contaminants that can lead to possible alterations to aquatic environments and affect human health, the effect of three operating parameters was studied (pH, the proportion of β-cyclodextrin polymer, and wastewater agitation). The proportion of β-cyclodextrin polymer and wastewater agitation had a favorable influence on drug extraction at 10 ppm. The PIMs containing β-cyclodextrin polymer was unstable in basic conditions and was more effective at acidic pH. These initial results demonstrate the high potential for drug extraction of this polymer.

Modeling and Optimization of the Drug Extraction Production Process

Optimized control of the drug extraction production process (DEPP) aims to reduce production costs and improve economic benefit while meeting quality requirements. However, optimization of DEPP is hampered by model uncertainty. Thus, in this paper, a strategy that considers model uncertainty is proposed. Mechanistic modeling of DEPP is first discussed in the context of previous work. The predictive model used for optimization is then developed by simplifying the mechanism. Optimization for a single extraction process is first implemented, but this is found to lead to serious wastage of herbs. Hence, the optimization of a multiextraction process is then conducted. To manage the uncertainty in the model, a data-driven iterative learning control method is introduced to improve the economic benefit by adjusting the operating variables. Finally, fuzzy parameter adjustment is adopted to enhance the convergence rate of the algorithm. The effectiveness of the proposed modeling and optimization strategy is validated through a series of simulations.