In vivo selection of novel biotherapeutics

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Apoferritin nanocage as drug reservoir: is it a reliable drug delivery system?

Apoferritin is a complex protein with a number of possibilities for drug delivery and drug targeting technologies, as it could be considered as the future self-assembling, not-toxic protein drug delivery carrier. Few years ago, this concept was a reality; nowadays, after more than 10 years of research, a clear painting of Apoferritin, loaded with drugs, is lacking, in terms of protocols of formulation, characterization, drug release and application. Therefore, a critical evaluation and overall understanding of Apoferritin is due to speed up the possibilities for its translatability into clinical application

Development and validation of a new storage procedure to extend the in-use stability of azacitidine in pharmaceutical formulations

Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment

The role of protamine amount in the transfection performance of cationic SLN designed as a gene nanocarrier

Cationic solid lipid nanoparticles (SLN) have been recently proposed as non-viral vectors in systemic gene therapy. The aim of this study was to evaluate the effect of the protamine amount used as the transfection promoter in SLN-mediated gene delivery. Three protamine-SLN samples (Pro25, Pro100, and Pro200) prepared by adding increasing amounts of protamine were characterized for their size, zeta potential, and protamine loading level. The samples were evaluated for pDNA complexation ability by gel-electrophoresis analysis and for cytotoxicity and transfection efficiency by using different cell lines (COS-I, HepG2, and Na1300). The size of SLN was ~230 nm and only Pro200 showed few particle aggregates. Unlike the Pro25 sample with the lowest protamine loading level, the others SLN samples (Pro100 and Pro200) exhibited a good ability in complexing pDNA. A cell-line dependent cytotoxicity lower than that of the positive control PEI (polyethilenimmine) was observed for all the SLN. Among these, only Pro100, having an intermediate amount of protamine, appeared able to promote pDNA cell transfer, especially in a neuronal cell line (Na1300). In conclusion, the amount of protamine as the transfection promoter in SLN affects not only the gene delivery ability of SLN but also their capacity to transfer genes efficiently to specific cell types

Dance Revolution: Long-Term Dance Generation with Music via Curriculum Learning

Dancing to music is one of human's innate abilities since ancient times. In machine learning research, however, synthesizing dance movements from music is a challenging problem. Recently, researchers synthesize human motion sequences through autoregressive models like recurrent neural network (RNN). Such an approach often generates short sequences due to an accumulation of prediction errors that are fed back into the neural network. This problem becomes even more severe in the long motion sequence generation. Besides, the consistency between dance and music in terms of style, rhythm and beat is yet to be taken into account during modeling. In this paper, we formalize the music-driven dance generation as a sequence-to-sequence learning problem and devise a novel seq2seq architecture to efficiently process long sequences of music features and capture the fine-grained correspondence between music and dance. Furthermore, we propose a novel curriculum learning strategy to alleviate error accumulation of autoregressive models in long motion sequence generation, which gently changes the training process from a fully guided teacher-forcing scheme using the previous ground-truth movements, towards a less guided autoregressive scheme mostly using the generated movements instead. Extensive experiments show that our approach significantly outperforms the existing state-of-the-arts on automatic metrics and human evaluation. We also make a demo video in the supplementary material to demonstrate the superior performance of our proposed approach.Comment: Accepted by ICLR 202

AFM phase imaging of soft-hydrated samples: A versatile tool to complete the chemical-physical study of liposomes

Despite of the several approaches applied to the physicochemical characterization of liposomes, few techniques are really useful to obtain information about the surface properties of these colloidal drug-delivery systems. In this paper, we demonstrate a possible new application of tapping mode atomic force microscopy (AFM) to discriminate between conventional and pegylated liposomes. We showed that the differences on liposomal surface properties revealed by the phase images AFM approach well correlate with the data obtained using classical methods, such as light scattering, hydrodynamic, and nuclear magnetic resonance analysis

Potential Use of Nanomedicine for Drug Delivery Across the Blood-Brain Barrier in Healthy and Diseased Brain

The research of efficacious non-invasive therapies for the treatment of brain diseases represents a huge challenge, as people affected by disorders of the central nervous system (CNS) will significantly increase. Moreover, the blood-brain barrier is a key factor in hampering a number of effective drugs to reach the CNS. This review is therefore focusing on possible interventions of nanomedicine-based approaches in selected diseases affecting the CNS. A wide overview of the most outstanding results on preclinical evaluations of the potential of nanomedicine in brain diseases (i.e. brain tumor, Alzheimer, Parkinson, epilepsy and others) is given, with highlights on the data with relevant interest and real possibility in translation from bench-to-bedside. Moreover, a critical evaluation on the rationale in planning nanosystems to target specific brain pathologies is described, opening the path to a more structured and pathology-tailored design of nanocarriers