Intensification of the freeze drying process by the control of both freezing and primary drying steps

The problem of optimization of freeze-drying cycles is addressed, with emphasis in both freezing and primary drying steps. In particular, this study shows that the control of the nucleation event produces more uniform batches (as ice nucleation is induced in all the vials of batch almost at the same time and temperature) and allows a marked reduction in the duration of the optimized cycle (if compared to cycles carried out with conventional stochastic nucleation

Intensification of the freeze drying process by the control of both freezing and primary drying steps

The problem of optimization of freeze-drying cycles is addressed, with emphasis in both freezing and primary drying steps. In particular, this study shows that the control of the nucleation event produces more uniform batches (as ice nucleation is induced in all the vials of batch almost at the same time and temperature) and allows a marked reduction in the duration of the optimized cycle (if compared to cycles carried out with conventional stochastic nucleation)

Effect of vacuum induced nucleation on the final product homogeneity

In the field of freeze drying of pharmaceutics the homogeneity of the sublimation flux during drying is fundamental to allow a final product with the same characteristics. Previous studies have shown that the control of freezing stage, in addition to a dramatic reduction of cycle duration, can also improve the homogeneity of the final batch. In this framework, this study is focused on the investigation of the effects of the Vacuum Induced Nucleation control method (modified in a previous work)[1,2] on the final structure of the product. Two aspects will be taken into consideration: the uniformity among vials of the same batch (inter-vial) and the uniformity of the structure along the height of the product (intra-vial). It has to be pointed out that a non-uniform product structure can have an impact on the protein aggregation and redistribution, and cause a partial cake collapse or micro-collapse. This investigation is really useful to define some limits of the control method used in this work

Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Abstract In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chromatography and cell-based potency assays have been used to characterize the formation of soluble aggregates and the biological activity of hGH, respectively. The results obtained indicate that controlled nucleation has a positive effect on both cycle performance and product homogeneity because of the formation of bigger ice crystals, and characterized by a narrower dimensional distribution. From the point of view of hGH stability, we observed that vacuum-induced surface freezing is not detrimental to the biological activity of the protein, or aggregate formation. In addition, the effect of 2 different formulations, including trehalose or cellobiose, on protein preservation was also considered for this study

At the cutting edge against cancer: A perspective on immunoproteasome and immune checkpoints modulation as a potential therapeutic intervention

Simple Summary:& nbsp;Immunoproteasome plays a key role in the generation of antigenic peptides. Immune checkpoints therapy is a front-line treatment of advanced/metastatic tumors, and to improve its efficacy, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is mandatory. The scope of this review is to offer a picture of the role of immunoproteasome in antigen presentation to fuel the hypothesis of novel therapeutic interventions based on the modulation of this proteolytic complex and immune checkpoints.Immunoproteasome is a noncanonical form of proteasome with enzymological properties optimized for the generation of antigenic peptides presented in complex with class I MHC molecules. This enzymatic property makes the modulation of its activity a promising area of research. Nevertheless, immunotherapy has emerged as a front-line treatment of advanced/metastatic tumors providing outstanding improvement of life expectancy, even though not all patients achieve a long-lasting clinical benefit. To enhance the efficacy of the currently available immunotherapies and enable the development of new strategies, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is needed. Therefore, a better understanding of the role of immunoproteasome in antigen processing and of the therapeutic implication of its modulation is mandatory. Studies on the potential crosstalk between proteasome modulators and immune checkpoint inhibitors could provide novel perspectives and an unexplored treatment option for a variety of cancers

Diagnostic accuracy of optical coherence tomography for diagnosing glaucoma: secondary analyses of the GATE study

Background/Aims: To assess the diagnostic performance of retinal nerve fibre layer (RNFL) data of optical coherence tomography (OCT) for detecting glaucoma. Methods: Secondary analyses of a prospective, multicentre diagnostic study (Glaucoma Automated Tests Evaluation (GATE)) referred to hospital eye services in the UK were conducted. We included data from 899 of 966 participants referred to hospital eye services with suspected glaucoma or ocular hypertension. We used both eyes’ data and logistic regression-based receiver operator characteristics analysis to build a set of models to measure the sensitivity and specificity of the average and inferior quadrant RNFL thickness data of OCT. The reference standard was expert clinician examination including automated perimetry. The main outcome measures were sensitivity at 0.95 specificity and specificity at 0.95 sensitivity and the corresponding RNFL thickness thresholds. We explored the possibility of accuracy improvement by adding measures of within-eye and between-eye variation, scan quality, intraocular pressure (IOP) and age. Results: Glaucoma was diagnosed in at least one eye in 17% of participants. Areas under the curve were between 0.83 and 0.88. When specificity was fixed at 0.95, the sensitivity was between 0.38 and 0.55, and the highest values were reached with models including the inferior quadrant rather than the average RNFL thickness. Fixing specificity at 0.95, the sensitivity was between 0.36 and 0.58. The addition of age, refractive error, IOP or within-subject variation did not improve the accuracy. Conclusion: RNFL thickness data of OCT can be used as a diagnostic test, but accuracy estimates remain moderate even in exploratory multivariable modelling of aiming to improve accuracy