An Industry Perspective on the use of Forced Degradation Studies to Assess Comparability of Biopharmaceuticals.

Forced degradation, also known as stress testing, is used throughout pharmaceutical development for many purposes including assessing the comparability of biopharmaceutical products according to ICH Guideline Q5E. These formal comparability studies, the results of which are submitted to health authorities, investigate potential impacts of manufacturing process changes on the quality, safety, and efficacy of the drug. Despite the wide use of forced degradation in comparability assessments, detailed guidance on the design and interpretation of such studies is scarce.

Achieving low-fouling surfaces with oppositely charged polysaccharides via LBL assembly.

Unlabelled: The aim of this work is to understand and achieve low fouling surfaces by mixing two oppositely charged polysaccharides through layer-by-layer (LBL) assembly. Diethylaminoethyl-dextran hydrochloride and alginate were employed as a model system to build LBL films. A surface plasmon resonance (SPR) biosensor was used to measure quantitatively the adsorption behavior of charged macromolecules during LBL buildup and the protein adsorption behavior of each deposited bilayer in situ in real time accordingly.

Achieving One-step Surface Coating of Highly Hydrophilic Poly(Carboxybetaine Methacrylate) Polymers on Hydrophobic and Hydrophilic Surfaces.

It is highly desirable to develop a universal nonfouling coating via a simple one-step dip-coating method. Developing such a universal coating method for a hydrophilic polymer onto a variety of surfaces with hydrophobic and hydrophilic properties is very challenging. This work demonstrates a versatile and simple method to attach zwitterionic poly(carboxybetaine methacrylate) (PCB), one of the most hydrophilic polymers, onto both hydrophobic and hydrophilic surfaces to render them nonfouling.

One-step dip coating of zwitterionic sulfobetaine polymers on hydrophobic and hydrophilic surfaces.

Zwitterionic sulfobetaine polymers with a catechol chain end (DOPA-PSB) were applied to a variety of hydrophobic polymer sheets and fibers. In addition, a silica surface was tested as a representative hydrophilic substrate. The polymer-coated surfaces showed significantly lower fouling levels than uncoated controls.

Sensitive and fast detection of fructose in complex media via symmetry breaking and signal amplification using surface-enhanced Raman spectroscopy.

A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group.

Biologically inspired stealth peptide-capped gold nanoparticles.

Introduction into the human body makes most nanoparticle systems susceptible to aggregation via nonspecific protein binding. Here, we developed a peptide-capped gold nanoparticle platform that withstands aggregation in undiluted human serum at 37 °C for 24 h. This biocompatible and natural system is based on mimicking human proteins which are enriched in negatively charged glutamic acid and positively charged lysine residues on their surface.

Free energy of solvated salt bridges: a simulation and experimental study.

Charged amino acids are the most common on surfaces of proteins and understanding the interactions between these charged amino acids, salt bridging, is crucial for understanding protein-protein interactions. Previous simulations have been limited to implicit solvent or fixed binding geometry due to the sampling required for converged free energies. Using well-tempered metadynamics, we have calculated salt bridge free energy surfaces in water and confirmed the results with NMR experiments.

Standardizing and simplifying analysis of peptide library data.

Peptide libraries allow researchers to quickly find hundreds of peptide sequences with a desired property. Currently, the large amount of data generated from peptide libraries is analyzed by hand, where researchers search for repeating patterns in the peptide sequences. Such patterns are called motifs.

Screening nonspecific interactions of peptides without background interference.

The need to discover new peptide sequences to perform particular tasks has lead to a variety of peptide screening methods: phage display, yeast display, bacterial display and resin display. These are effective screening methods because the role of background binding is often insignificant. In the field of nonfouling materials, however, a premium is placed on chemistries that have extremely low levels of nonspecific binding.

Sequence, structure, and function of peptide self-assembled monolayers.

Cysteine is commonly used to attach peptides onto gold surfaces. Here we show that the inclusion of an additional linker with a length of four residues (-PPPPC) and a rigid, hydrophobic nature is a better choice for forming peptide self-assembled monolayers (SAMs) with a well-ordered structure and high surface density. We compared the structure and function of the nonfouling peptide EKEKEKE-PPPPC-Am with EKEKEKE-C-Am.