ABSTRACT
Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell-cell communication in a wide range of embryonic developmental processes and in fetal-maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood-brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., "liquid biopsies", but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed.
Subject(s)
Axons/metabolism , Cell-Derived Microparticles/metabolism , Exosomes/metabolism , Nervous System Diseases/metabolism , Neural Stem Cells/metabolism , Amyotrophic Lateral Sclerosis/metabolism , Blood-Brain Barrier/metabolism , Cell Communication , Dental Pulp/cytology , Dental Pulp/metabolism , Female , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Nervous System Diseases/diagnosis , Nervous System Diseases/prevention & control , Neural Stem Cells/cytology , Placenta/metabolism , Pregnancy , Regeneration/geneticsABSTRACT
An electrospinning process was optimized to produce fibers of micrometric size with different combinations of polymeric and surfactant materials to promote the dissolution rate of an insoluble drug: firocoxib. Scanning Electron Microscopy (SEM) showed that only some combinations of the proposed carrier systems allowed the production of suitable fibers and further fine optimization of the technique is also needed to load the drug. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) suggest that the drug is in an amorphous state in the final product. Drug amorphization, the fine dispersion of the active in the carriers, and the large surface area exposed to water interaction obtained through the electrospinning process can explain the remarkable improvement in the dissolution performance of firocoxib from the final product developed.
Subject(s)
4-Butyrolactone/analogs & derivatives , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/chemistry , Drug Carriers , Nanofibers , Polymers , Sulfones/administration & dosage , Sulfones/chemistry , Surface-Active Agents , 4-Butyrolactone/administration & dosage , 4-Butyrolactone/chemistry , Drug Carriers/chemistry , Nanofibers/chemistry , Nanofibers/ultrastructure , Polymers/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , Surface-Active Agents/chemistry , ThermodynamicsABSTRACT
The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of biopharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. The functional groups involved in the interaction leading to cocrystals formation were investigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug.
Subject(s)
Calorimetry, Differential Scanning , Chemistry, Pharmaceutical/methods , Hypoglycemic Agents/pharmacokinetics , Nateglinide/pharmacokinetics , Administration, Oral , Drug Liberation , Hydrogen-Ion Concentration , Hypoglycemic Agents/analysis , Hypoglycemic Agents/chemistry , Nateglinide/analysis , Nateglinide/chemistry , Powder Diffraction , Solubility , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
20-(S)-Camptothecin (CPT) is a natural alkaloid extracted from the bark of Camptotheca acuminata (Chinese happy tree). It acts as a DNA topoisomerase 1 poison with an interesting antitumor activity and its use is limited by low stability and solubility and unpredictable drug-drug interactions. Since the late 20th century, it has been widely used in cancer therapy and, since extraction yields from plant tissues are very low, various synthetic routes have been developed to satisfy the increase in demand for CPT. Moreover, SAR studies have allowed for the development of more potent CPT analogues topotecan and irinotecan. Unfortunately, resistance has already occurred in several tumour lines. Additional studies are needed to better understand the relationship between substituents and resistance, its clinical relevance and the impact of related gene polymorphism. One of the latest research approaches focuses on modifying the delivery mode to improve tumour cell uptake and reduce toxicity.
