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"Therapeutics delivery"
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Next RNA Therapeutics: The Mine of Non-Coding
The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application.
Journal Article
Nanoparticle formulations for therapeutic delivery, pathogen imaging and theranostic applications in bacterial infections
Pathogenic bacterial infections represent an ever-growing crisis, now significantly threatening life expectancy across the worldwide population and thus novel approaches to tackle this issue are urgently needed. The application of nanotechnology in recent years has opened up new horizons in the selective or specific delivery of drugs or imaging agents to infectious sites. In particular, the development of nanoparticles for both delivery of active substances and imaging of infection sites is now gathering much interest. Although still in its infancy, the field of antibacterial nanomedicines provides exciting new possibilities to combat multi-resistant bacterial infections and shows great promise for personalized medicine in antibacterial stewardship. This review examines nanoparticle-based formulations used for therapeutic delivery, pathogen tracking in diagnosis, and combined \"theranostic\" approaches to more effectively treating bacterial infections.
Journal Article
Lipid membrane-camouflaged biomimetic nanoparticle for MicroRNA based therapeutic delivery to intestinal epithelial cells
We have made artificial extracellular vesicles like nanoparticles that contain biologically active Agomir (miRNA mimic)/Antagomir (miRNA inhibitor) adsorbed on magnetic ZnO particles bound by a lipid bilayer membrane from Caco-2 cells (human colorectal adenocarcinoma), which we examined for use as therapeutic nanoparticles or as delivery vehicles for therapeutic agents to the gut epithelia. Magnetic ZnO nanoparticles were synthesized using Manganese doping in both solid-state reaction (SSR) and alkaline aqueous solution methods. The SSR method exhibited ferromagnetic behavior, whereas the alkaline solution method yielded a nanorod-like morphology. Encapsulation was demonstrated using mercaptosuccinic acid. These biocompatible nanoparticles, owing to their nanorod-like morphology with larger surface area, were used to adsorb miR200c antagomir/agomir molecules as well as assemble lipid membrane fragments from Caco-2 cells. We performed various in vivo efficacy studies of Caco-2 NanoVesicles (CNVs) (Caco-2NanoVesicles) or detrimental CNV (therapeutic Caco-2 NanoVesicles (tCNVs)) loaded with miR200c Agomir that degrade occludin protein-coding mRNA as a proof of concept for clinical use of the Antagomir counterpart. There was no discernible toxicity, mortality, or systemic inflammatory or immunological responses in mice following administration of either CNVs or tCNVs. tCNV administration enhances intestinal permeability in mice. This supports their use as biological Nano-therapeutics to restore the gut barrier.
Journal Article
Empowering Precision Medicine: The Impact of 3D Printing on Personalized Therapeutic
This review explores recent advancements and applications of 3D printing in healthcare, with a focus on personalized medicine, tissue engineering, and medical device production. It also assesses economic, environmental, and ethical considerations. In our review of the literature, we employed a comprehensive search strategy, utilizing well-known databases like PubMed and Google Scholar. Our chosen keywords encompassed essential topics, including 3D printing, personalized medicine, nanotechnology, and related areas. We first screened article titles and abstracts and then conducted a detailed examination of selected articles without imposing any date limitations. The articles selected for inclusion, comprising research studies, clinical investigations, and expert opinions, underwent a meticulous quality assessment. This methodology ensured the incorporation of high-quality sources, contributing to a robust exploration of the role of 3D printing in the realm of healthcare. The review highlights 3D printing's potential in healthcare, including customized drug delivery systems, patient-specific implants, prosthetics, and biofabrication of organs. These innovations have significantly improved patient outcomes. Integration of nanotechnology has enhanced drug delivery precision and biocompatibility. 3D printing also demonstrates cost-effectiveness and sustainability through optimized material usage and recycling. The healthcare sector has witnessed remarkable progress through 3D printing, promoting a patient-centric approach. From personalized implants to radiation shielding and drug delivery systems, 3D printing offers tailored solutions. Its transformative applications, coupled with economic viability and sustainability, have the potential to revolutionize healthcare. Addressing material biocompatibility, standardization, and ethical concerns is essential for responsible adoption.
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Journal Article
Controlling endosomal escape using nanoparticle composition: current progress and future perspectives
Polymer nanoparticles offer significant benefits for improving delivery of biological therapeutics such as DNA and proteins, as they allow the cargo to be protected until it is delivered to a target cell. However, there are still challenges with achieving efficient delivery to the optimal cellular region. One significant roadblock is escape of nanoparticles from within the endosomal/lysosomal compartments into the cytosol. Here, we review the recent advances in understanding endosomal escape of polymer nanoparticles. We also discuss the current progress on investigating how nanoparticle structure can control endosomal escape. It is important to understand the fundamental biological processes that govern endosomal escape in order to design more effective therapeutic delivery systems.
Journal Article
Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core
Most therapeutic agents are excluded from entering the central nervous system by the blood–brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf–TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.
Journal Article
Formulations for Bacteriophage Therapy and the Potential Uses of Immobilization
The emergence of antibiotic-resistant pathogens is becoming increasingly problematic in the treatment of bacterial diseases. This has led to bacteriophages receiving increased attention as an alternative form of treatment. Phages are effective at targeting and killing bacterial strains of interest and have yielded encouraging results when administered as part of a tailored treatment to severely ill patients as a last resort. Despite this, success in clinical trials has not always been as forthcoming, with several high-profile trials failing to demonstrate the efficacy of phage preparations in curing diseases of interest. Whilst this may be in part due to reasons surrounding poor phage selection and a lack of understanding of the underlying disease, there is growing consensus that future success in clinical trials will depend on effective delivery of phage therapeutics to the area of infection. This can be achieved using bacteriophage formulations instead of purely liquid preparations. Several encapsulation-based strategies can be applied to produce phage formulations and encouraging results have been observed with respect to efficacy as well as long term phage stability. Immobilization-based approaches have generally been neglected for the production of phage therapeutics but could also offer a viable alternative.
Journal Article
Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration
Bone injuries and diseases constitute a burden both socially and economically, as the consequences of a lack of effective treatments affect both the patients’ quality of life and the costs on the health systems. This impended need has led the research community’s efforts to establish efficacious bone tissue engineering solutions. There has been a recent focus on the use of biomaterial-based nanoparticles for the delivery of therapeutic factors. Among the biomaterials being considered to date, calcium phosphates have emerged as one of the most promising materials for bone repair applications due to their osteoconductivity, osteoinductivity and their ability to be resorbed in the body. Calcium phosphate nanoparticles have received particular attention as non-viral vectors for gene therapy, as factors such as plasmid DNAs, microRNAs (miRNA) and silencing RNA (siRNAs) can be easily incorporated on their surface. Calcium phosphate nanoparticles loaded with therapeutic factors have also been delivered to the site of bone injury using scaffolds and hydrogels. This review provides an extensive overview of the current state-of-the-art relating to the design and synthesis of calcium phosphate nanoparticles as carriers for therapeutic factors, the mechanisms of therapeutic factors’ loading and release, and their application in bone tissue engineering.
Journal Article
Synthesis of polymeric nanoparticles by double emulsion and pH-driven: encapsulation of antibiotics and natural products for combating Escherichia coli infections
The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against
Escherichia coli
underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by
E. coli.
Key points
• The double emulsion method provides control over size and release of bioactives.
• The pH-driven method improves the solubility, stability, and release of active.
• The methods increase the antibacterial action of those encapsulated in PNPs.
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Journal Article