1,721,031 research outputs found
Nanomedicine: the future for advancing medicine and neuroscience
No full textConsidering the last half century, the delivery of pharmacologically active substances, such as synthetic drugs, natural compounds, gene material and many other pharmaceutical products, has been widely studied and investigated [1]. Scientists working on the field of pharmacological active substances easily understood that the main problem of such molecules is represented by their wide and non-specific biodistribution once administered in the human body. This reflect in an increase in toxicity and contemporaneously in both a decreased patient’s compliance and decreased benefit-risk ratio. Another critical issue consists of the tremendous difficulty of such drugs and active molecules in crossing biological barriers [2]. In this view, the development of drug delivery systems (DDS) is aimed to create carriers able to improve the pharmacokinetic profile of drugs. Along with this purpose, the carriers could protect the body from the exposure of a great amount of drugs thus decreasing the circulating doses. Taken together, these aspects surely represent one of the most innovative improvement of the last decade of pharmaceutical research. This strategy took the smart name of “Nanomedicine”, mainly based on the use of lipid-based (liposomes, LPs), polymer-based (nanoparticles, NPs) nanocarriers or metal-based nanovectors. The last example of nanocarriers (i.e. super-paramagnetic nanoparticles) are currently applied in medicine in order to improve the quality and the specificity of body/cell imaging and diagnostic. These carriers are usually made of gold or iron, featured by a core-shell able to be visualized in body depth, thus allowing the physician to obtain better defined contrast and diagnostic images. Some examples are Resovist ® (Shering, Berlin, Germany) and Endorem/Lumirem ® (Advanced Magnetics, Guebert, France) used for liver tumor imaging. Considering the drug delivery and drug targeting aim deputed to Nanomedicine, the main advantages of nanocarriers rely on the protection of the active molecule from the metabolism and degradation, the possibility of governing the drug release over time and the ability in reaching target site (mainly organ or tissue) by using passive-route. Despite these applications, which encourages highlights from the researches, the main limits that may hamper the development of such nanocarriers could be recognized in the lack of selectivity and specificity of DDS. Thus, in order to maximize the therapeutic effect, the new “smart” DDS need to be further engineered to obtain “stable and ultra-selective” carriers able to deliver the drugs not only to the target organ or tissue but also to the target cell. In fact, in the last 10 years, the research in Nanomedicine strongly focused on the use of specific ligands (antibodies, peptides, substrates of receptors, and many others) to be conjugated onto the surface of NPs and LPs, thus enabling nanocarriers to specifically target cell population or to cross virtually impermeable barriers, as the Blood Brain Barrier [2].Some important focuses should be considered when approaching to Nanomedicine, such as its development in comparison with other innovative approaches (i.e. personalized medicine) and its application to the most difficult-to-treat diseases (i.e. neurodegenerative and neurological disorders)
Apoferritin nanocage as drug reservoir: is it a reliable drug delivery system?
No full textApoferritin 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
The bridge between Nanotechnology and Neuroscience: Neuro-Nanomedicine
No full textThe application of nanotechnology to the field of medicine is now at the cutting edge of scientific research. Named as Nanomedicine, this smart strategy is aimed to find new approaches for therapeutic application in the difficult-to-treat pathologies, as neurological diseases. Applied to Central Nervous System (CNS) pathologies, nanocarriers, engineered for the specific passage across the Blood-Brain Barrier (BBB), have been widely studied with stimulating and interesting results. The in vivo and in vitro experiments clearly demonstrated the potential of this kind of approach, that, now, clearly needs a higher grade of translation of the research to preclinical model of pathologies. This paper provides for an incisive description of the rationale and the development of nanomedicine applied to neuroscience, the neuro-nanomedicine
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Immunoliposomes for the delivery of SiRNA and chemioterapeutic agent to primary effusion lymphoma
No full textBreve descrizione delle metodologie attuate per promuovere il rilascio di farmaci e materiale genico al tumore. In particolare è stato discusso l'approccio con liposomi e sistemi lipidic
NANOPARTICELLE DIREZIONANTI AL CERVELLO: RIPRISTINO DEI LIVELLI DI COLESTEROLO CELLULARE NELLA TERAPIA DELLA COREA DI HUNTINGTON.
No full textIl colesterolo svolge un ruolo fondamentale sia strutturale che funzionale nel mantenimento delle attività cellulari cerebrali, con notevoli implicazioni nella regolazione del trafficking cellulare, della trasduzione del segnale e della sintesi della mielina. Alterazioni nella omeostasi del colesterolo sono spesso causa di patologie neurodegenerative, come la Corea di Huntington, una grave patologia del sistema nervoso centrale (SNC) che colpisce specificamente i neuroni del corpo striato e si manifesta con disfunzioni motorie, alterazioni cognitive e comportamentali. L’implementazione del colesterolo, con l’apporto di colesterolo esogeno a livello del SNC appare pertanto come un approccio proponibile nel trattamento combinato di tali patologie.
Purtroppo, il colesterolo tal quale non supera la barriera ematoemcefalica (BEE) in quantità efficaci. Per veicolare colesterolo al SNC, è stata proposta la formulazione di nanoparticelle polimeriche (Nps) caricate con colesterolo (CHOL) e modificate in superficie con un epatpeptide (g7) capace di promuovere il superamento della BEE.
Inizialmente sono state allestite Nps variando diversi parametri
formulativi quali il rapporto CHOL/PLGA, la tecnica di purificazione, l’impiego di tensioattivo nella formulazione e di crioprotettori nella fase di stabilizzazione (tipo, quantità etc..); tale studio tecnologico ha permesso di ottenere un sistema riproducibile, con un adeguato caricamento, una buona resa e stabile alla conservazione.
Successivamente le Nps, rese tracciabili attraverso l’impiego di piccole percentuali di polimero coniugato con rodamina e caricate con colesterolo a sua volta marcato con un diverso fluorocromo (CHOLNBD), sono state somministrate IP in topi sani e modelli di Huntington (R6/2). Studi di microscopia confocale hanno dimostrato la presenza di significative concentrazioni di Nps e di colesterolo a livello celebrale, nonchè l’abilità di tali sistemi nel promuovere un rilascio sostenuto del farmaco per almeno due settimane
Formulazione di siRNA anti blimp-1/PRDM in liposomi cationici: caratterizzazione chimico-fisica e validazione in vitro su cellule di LINFOMA EFFUSIVO PRIMARIO (pel)
No full textFormulazione di siRNA anti blimp-1/PRDM in liposomi cationici: caratterizzazione chimico-fisica e validazione in vitro su cellule di LINFOMA EFFUSIVO PRIMARIO (pel
AFM and TEM characterization of siRNAs lipoplexes: a combinatory tools to predict the efficacy of complexation
No full textThis work aims to evaluate the effects of two different surface modification strategies: PEG conventional coupling (PEG-Lpx) and postpegylation technique (postPEG-Lpx), on lipoplexes obtained between liposomes and siRNAs. Photon correlation spectroscopy (PCS) and gel electrophoreses (as conventional techniques), and atomic force microscopy (AFM) and transmission electron microscopy (TEM) (proposed to complete the assessments of
lipoplexes) were employed to investigate reorganization, structure, qualitative-quantitative stabilization of siRNAs, and PEG covering of lipoplexes. The results suggested that postPEGLpx
exhibited high level of homogeneity with a mean diameter (Z-Average) of about 320 nm, low tendency to aggregation (a polydispersion index, PDI, close to 0.06) and high loading
efficiency (E.E. 82%). Otherwise, PEG-Lpx showed a Z-Average greater than 1m, high aggregation rate (PDI > 0.3) and a low E.E. (10%). The definition of the architecture by using optimized microscopical procedure allows to suggest postpegylation technique as a promising technology for the preparation of applicable complexes. This formulation strategy lead to a
stable siRNA condensation and full compaction of gene material, moreover the PEG coverage generated a homogeneous hydrated surface, well described by the ―phase‖ AFM approach.
The microscopical techniques can provide a predictive and useful tool to use in the preformulative technological studies of complicated gene complexes
Nanoparticle transport across the blood brain barrier
No full textABSTRACT: While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes
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