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Optimized and Simplified Technique for the Production and Culture of Precision-Cut Liver Slices

This protocol presents a simple system for the creation and culture of Precision-cut Liver Slices (PCLS). PCLS contains all cells in an intact environment ...

University College London

Thermal ink-jet spray freeze-drying (TIJ-SFD) was used to produce inhalable particles of terbutaline sulphate, the aerosolisation properties of which were compared to the commercial Bricanyl formulation. Scanning electron micrograph images showed the particles to be spherical, highly porous and suitable for aerosolisation from a simple, capsule-based dry-powder device (Cyclohaler) without the need for additional excipients. Particle size was dependent upon the concentration of solution jetted, as well as the distance between the print head and the surface of the liquid nitrogen. Starting with a 5% (w/v) solution and maintaining this distance at 3cm produced spherical, porous particles of volume median diameter (VMD) 14.1 ± 0.8 μm and mass median aerodynamic diameter (MMAD) 4.0 ± 0.6 μm. The fine particle fraction (proportion of aerosol with MMAD ≤ 4.46 μm) was 22.9 ± 3.3%, which compared favourably with that of the marketed dry powder inhaler formulation of terbutaline (Bricanyl Turbohaler; 25.7 ± 3.8%), tested under the same conditions. These findings show that TIJ-SFD is a useful tool to predict the viability of a DPI formulation during preformulation physicochemical characterisation.

In vitro characterisation of terbutaline sulphate particles prepared by thermal ink-jet spray freeze drying.

When formulated as liquid dosage forms, therapeutic proteins and peptides often show instability during handling as a result of chemical degradation. Solid formulations are frequently required to maintain protein stability during storage, transport and upon administration. Herein we highlight current strategies used to formulate pharmaceutical proteins in the solid form. An overview of the physical instabilities which can arise with proteins is first described. The key solidification techniques of crystallization, freeze-drying and particle forming technologies are then discussed. Examples of current commercial products that are formulated in the solid state are provided and include neutral protamine Hagedorn - insulin crystal suspensions, freeze-dried monoclonal antibodies and leuproride polylactide-co-glycolide microparticles. Finally, future perspectives in solid-state protein formulation are described.

Solid-state protein formulations.

In academic research and the pharmaceutical industry,  cell lines and  animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have intrinsic limitations, whilst the use of precision-cut tissue slices can bridge the gap between these mainstream models. Precision-cut tissue slices combine the advantage of high reproducibility, studying all cell sub-types whilst preserving the tissue matrix and extracellular architecture, thereby closely mimicking a mini-organ. This approach can be used to replicate the biological phenotype of liver monogenic diseases using mouse models.

Article	Year
In vitro characterisation of terbutaline sulphate particles prepared by thermal ink-jet spray freeze drying. International journal of pharmaceutics\| PubMed ID: 23454848	2013
Solid-state protein formulations. Therapeutic delivery\| PubMed ID: 25565441	2015
precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases. F1000Research\| PubMed ID: 38618017	2023

Garima Sharma

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