A high-flux backscattering spectrometer and a time-of-flight disk chopper spectrometer are used to probe the molecular mobility of model freeze-dried phospholipid liposomes at a range of temperatures surrounding the main melting transition. Using specific deuteration, quasielastic neutron scattering provides evidence that, in contrast to the hydrocarbon chains, the headgroups of the phospholipid molecules do not exhibit a sharp melting transition. The onset of motion in the tails is located at temperatures far below the calorimetric transition. Long-range motion is achieved through the onset of whole-lipid translation at the melting temperature. Atomistic simulations are performed on a multibilayer model at conditions corresponding to the scattering experiments. The model provides a good description of the dynamics of the system, with predictions of the scattering functions that agree with experimental results. The analysis of both experimental data and results of simulations supports a picture of a gradual melting of the heterogeneous hydrophobic domain, with part of the chains spanning increasingly larger volumes and part of them remaining effectively immobile until the thermodynamic phase transition occurs.
The continuous increase in the number of approved monoclonal antibody (mAb)-based therapy suggests that mAbs, and their derivatives, will continue to be the focus of the biotherapeutics industry for years to come. Although vast improvements in our capability to manufacture, characterize, and stabilize mAbs have been achieved, there are still challenges to be overcome. These include analytical and stabilization approaches associated with the development of high concentration mAb formulations. In addition, several mAb-based modalities are under development, including antibody drug conjugates (ADCs), fusion proteins, and bispecific antibodies (bsAbs), all designed to overcome the limitations encountered with mAb therapy. The current status of their development, with emphasis on manufacturing challenges as well as preliminary clinical results, will be reviewed
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