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Background and Objectives : Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood-brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), particularly poly(lactic-co-glycolic acid) (PLGA) NPs, hold an outstanding position due to their biocompatible and biodegradable qualities. Despite their potential, the translation of PLGA NPs from laboratory-scale production to clinical applications remains a significant challenge. This study aims to address these limitations by developing scalable PLGA NPs and evaluating their potential biological applications. Methods : We prepared blank and model-protein-loaded (albumin-FITC and wheat germ agglutinin-488 (WGA-488)) fluorescent PLGA NPs using the traditional double-emulsion method combined with the micro-spray-reactor system, a novel approach that enables fine particle production enabling scale-up applications. We tested the biocompatibility of the NPs in living RPMI 2650 and neuroblastoma cell lines, as well as their trafficking and uptake. Release kinetics of the encapsulated proteins were investigated through confocal microscopy and in vitro release studies, providing insights into the stability and functionality of the released proteins. Results : The formulation demonstrated sustained and prolonged protein release profiles. Importantly, cellular uptake studies revealed that the NPs were not internalized. Furthermore, encapsulated WGA-488 protein retained its functional activity after release, validating the integrity of the encapsulation and release processes. Conclusions : The proof-of-concept study on NP manufacturing and an innovative drug trafficking and release approach can bring new perspectives on scalable preparations of PLGA NPs and their biological applications.

Most stars in today's Universe reside within spheroids, which are bulges of spiral galaxies and elliptical galaxies 1,2 . Their formation is still an unsolved problem 3-5 . Infrared/submillimetre-bright galaxies at high redshifts 6 have long been suspected to be related to spheroid formation 7-12 . Proving this connection has been hampered so far by heavy dust obscuration when focusing on their stellar emission 13-15 or by methodologies and limited signal-to-noise ratios when looking at submillimetre wavelengths 16,17 . Here we show that spheroids are directly generated by star formation within the cores of highly luminous starburst galaxies in the distant Universe. This follows from the ALMA submillimetre surface brightness profiles, which deviate substantially from those of exponential disks, and from the skewed-high axis-ratio distribution. Most of these galaxies are fully triaxial rather than flat disks: the ratio of the shortest to the longest of their three axes is half, on average, and increases with spatial compactness. These observations, supported by simulations, reveal a cosmologically relevant pathway for in situ spheroid formation through starbursts that is probably preferentially triggered by interactions (and mergers) acting on galaxies fed by non-coplanar gas accretion streams., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Central nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood-brain barrier. While protecting the brain's homeostasis, the barrier limits the passage of almost all large-molecule drugs and most small-molecule drugs. A noninvasive method, nose-to-brain delivery (N2B delivery) has been proposed to overcome this challenge. By exploiting the direct anatomical interaction between the nose and the brain, the drugs can reach the target, the brain. Moreover, the drugs can be encapsulated into various drug delivery systems to enhance physicochemical characteristics and targeting success. Many preclinical data show that this strategy can effectively deliver biopharmaceuticals to the brain. Therefore, this review focuses on N2B delivery while giving examples of different drug delivery systems suitable for the applications. In addition, we emphasize the importance of the effective delivery of monoclonal antibodies and RNA and stress the recent literature tackling this challenge. While giving examples of nanotechnological approaches for the effective delivery of small or large molecules from the current literature, we highlight the preclinical studies and their results to prove the strategies' success and limitations., (Copyright © 2024, Akpinar Adscheid et al.)