Purpose: To design, formulate and characterize sustained-release formulations of dexketoprofen trometamol (DT) nanoparticles (NPs) Methods: Dexketoprofen trometamol (DT)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs were produced by double emulsion-solvent evaporation method. The NPs were variously characterized for drug loading and release, particle profile, as well as by thermal analysis, x-ray difraction (XRD), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance analysis (1 H-NMR). Furthermore, the NPs were evaluated for cytotoxicity against NIH-3T3 cells by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The DT-loaded NPs demonstrated nanostructural characteristics and extended drug release. Particle size was in the range of 243 and 295 nm which remained unchanged in drug stability testing in simulated gastrointestinal media. Encapsulation efficiency ranged from 49-64 % for all the formulations. Higuchi and Korsmeyer-Peppas were the best-fit release kinetic models for the NPs containing 5 and 10 % DT, respectively. The NPs with 10 % DT presented no significant cytotoxicty at the doses and periods studied. Conclusion: Stable and non-toxic DT NPs with potential for sustained and controlled release of the drug have been successfully developed.
Neurodegenerative diseases, like Alzheimer´s and Parkinson´s disease, are a group of disorders that have in common their increasingly high prevalence along with the shortage of effective treatments. In addition, the scientific community faces the challenge of getting the drugs used in these treatments to cross the blood-brain barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. Hence, researchers across multiple disciplines are working together in order to improve the ability of therapeutics to penetrate the BBB. In this sense, the use of nanomedicine, nanoscale structures for drug delivery, exhibits a really high therapeutic potential in the field of neurodegenerative diseases therapy. Since there is new evidence that neuroinflammation produced by reactive microglia contributes to the activation and pathogenesis of neurological disorders, many investigations focus on the identification of new targets whose inhibition can reduce, totally or partially, microglial activation. This review analyzes a wide variety of compounds as possible candidates to achieve this target, from compounds with a natural origin to anti-diabetics, antidepressants, antibiotics and hormones. We also discuss the different strategies to enhance the capacity of these compounds to cross the BBB. Although this review focuses on PLGA nanoparticles as one of the most versatile drug delivery nanosystems, we also describe other strategies, such as direct intranasal administration (nose-tobrain), novel viral vectors and novel implanted catheters.
Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX’s mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.
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