1,720,991 research outputs found
Biocompatible nanocarriers for delivering drugs to skeletal muscle cells: a therapeutic option for myotonic dystrophy?
Full text linkMyotonic dystrophy (DM) represents a genetic disorder characterized by progressive dysfunction of multiple organs and tissues (e.g. skeletal, cardiac, and smooth muscle; the central nervous systems) among which the most severely affected is the skeletal muscle; this condition leads patients to a progressive muscle weakness, wasting and myotonia. The molecular pathogenetic mechanism of DM type 1 (or Steinert’s) disease is the expansion of a (CTG)n triplet in 3’ UTR region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, while the (CCTG)n quadruplet expansion in the first intron of the cellular Nucleic Acid Binding Protein/Zinc Finger 9 (CNBP/ZNF9) is responsible for DM type 2 (previously named “proximal Myotonic Myopathy” or “PROMM”). These expanded repeats are transcribed into toxic RNA that accumulates in nuclear RNA-protein aggregates (called foci), and lead to a general splicing alteration. The main problem of DM pathologies is that no therapies are currently available, and the commonly used treatments are administered to only manage symptoms. At present, the pharmaceutical research is screening small molecules such as pentamidine (PTM) able to repair the DM-associated splicing defects: PTM is an antimicrobial and antitumor compound that can mitigate the DM missplicing, but has limited applicability in humans due to its high systemic toxicity. To overcome these limitations, the administration via biocompatible nanoparticles (NPs) may represent a suitable approach, improving targeted delivery of the therapeutic drug and decreasing its systemic toxicity. Therefore, the main goal of the present experimental thesis was to set up an innovative experimental therapeutic strategy for DM based on biocompatible NPs loaded with PTM. To this aim, different types of NPs potentially suitable for drug delivery [liposomes, poly(lactic-co-glycolic acid) (PLGA) NPs, mesoporous silica NPs] were tested for biocompatibility in vitro on stabilized tumor cell lines and cultured primary human muscle cells. Conventional and confocal fluorescence microscopy and transmission electron microscopy allowed elucidating the mechanisms of NP internalization, intracellular distribution, fate and degradation. The tested NPs proved to be biocompatible for all the cell types investigated, although muscle-derived cells (especially the differentiated myotubes) showed lower internalization capability than cancer cells. In addition, novel hyaluronic acid-based nanocomplexes for hydrophilic drug encapsulation were synthesized in collaboration with the University of Lyon; these NPs proved to be biocompatible for both cancer and cultured muscle cells, and to efficiently deliver PTM to cancer cells; the effects of PTM-loaded NPs on muscle cells are currently under investigation. Finally, in the attempt to fill the gap between the conventional cell cultures and the organ complexity in vivo, an in vitro fluid dynamic system was set up to improve the preservation of explanted muscles and was then used for monitoring the biodistribution of NPs in this organ. Preliminary results revealed that PLGA NPs, which are easily internalized by cultured muscle cells, hardly enter the myofibers in the whole muscle since most of them accumulate in the connective tissue; consequently, modifications of the NP surface are in progress to improve targeting to and uptake by the muscle fibers
Special Issue: "Application of Nanotechnology in Regenerative Medicine"
Full text linkRegenerative medicine is a relatively young field, born as a convergence of disparate disciplines aimed at restoring or replacing tissues and organs [...]
Monitoring the uptake and intracellular fate of nanovectors by microscopical technique
No full textNanovectors are receiving great attention for their potential in therapeutic and diagnostic applications as innovative systems for drug delivery and medical imaging. Their unique features allow them to pass through the biological barriers, to accumulate at the target sites, to protect the loaded drugs from enzymatic degradation and to modulate their release. To design effective and safe administration procedures of nanovectors it is obviously mandatory to assess their possible cytotoxicity, but it is also essential to elucidate the uptake mechanism(s), the intracellular trafficking pathway, the interactions with cell organelles and the intracellular persistence of nanovectors, paying particular attention to their degradation routes. Microscopy is especially suitable to describe the interaction of nanocarriers with the cell surface and their intracellular fate following internalization. Fluorochrome-labelled nanoparticles may be observed by conventional and confocal fluorescence microscopy, while the higher resolution of transmission electron microscopy allows to reveal the specific relationships of nanocomposites with the subcellular constituents. This work summarizes some studies performed by different microscopical techniques to evaluate the properties of nanoparticles intended for therapeutic and diagnostic purposes
Nanocarriers for Medical Ozone Delivery: A New Therapeutic Strategy
Full text linkOzone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O3 doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O3 make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O3 is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O3. In recent years, novel O3 formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O3, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O3 and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O3 through nanocarriers is a just-started challenge, and multiple prospects may be foreseen
Microscopy techniques in nanomedical research
No full textIn recent years, the application of nanotechnology to biomedicine has been exponentially increasing. The physical and chemical properties, quality and safety of nanomaterials designed for biomedical application need to be accurately evaluated by means of reliable and robust techniques. Among the methods used, microscopy techniques play a primary role. This paper presents a brief overview of the contribution of different microscopy techniques to the study of the structural and functional aspects of nanoconstructs and their relationships with the biological milieu, demonstrating the great impact that microscopy sciences have in nanomedical research and applications
Nanotechnological research for regenerative medicine: the role of hyaluronic acid
Full text linkHyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology
In Vitro and Ex Vivo Models to Study Molecular Trafficking Across the Human Intestinal Barrier
Full text linkThe intestine is a complex organ whose main functions are food digestion and nutrient absorption. It is therefore of great interest for pharmaceutical research as a preferred route for drug delivery. In vitro intestinal models are valuable tools for the preclinical evaluation of absorption, distribution, metabolism, and excretion of new therapeutic formulations; consequently, several attempts have been made to recreate the human intestine barrier in vitro. The models so far set up were aimed at mimicking specific intestinal features related to the molecules or processes under investigation. Artificial membranes are suitable to study passive absorption; systems based on 2D/3D cell cultures reproduce the transcellular pathway; organs-on-a-chip mimic the in vivo cellular and mechanical complexity, allowing the identification of the multiple factors involved in molecular interactions with the intestinal barrier; and intestine explants replicate in full the native organ under controlled conditions, thus providing the most comprehensive in vitro model. All these models have advantages and disadvantages but all have given important contribution to advance the knowledge on the interaction of drugs, toxins, and xenobiotic with the intestinal barrier
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