RESUMEN
Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physicoâ»chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 µg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.
RESUMEN
Abstract Many people use medicinal plants to relieve disorders related to the central nervous system, such as depression, epilepsy, anxiety and pain, even though the effectiveness of most of them has not yet been proven through scientific studies. Plants of the Lippia genus, Verbenaceae, are widely used in ethnobotany as a food, for seasoning and in antiseptic remedies. They are also marketed and used for the treatment of different types of pain, including stomach ache, abdominal pain and headache, as well as being used as sedatives, anxiolytics and anticonvulsants. Despite their widespread use, there are no reviews on the central nervous system profile of plants of this genus. Therefore, the databases Medline-PubMed, Embase, Scopus and Web of Science were searched using the terms Lippia and biologic activity. Thirty-five papers were found. Eleven species of Lippia showed central nervous system activity, with leaves and the aerial parts of plants being the most commonly used, especially in aqueous and ethanol extracts or volatile oil. The species are composed mainly of terpenoids and phenylpropanoids, including polyketides, flavonoids and in less quantity some alkaloids. Although several species of Lippia present analgesic activity, most studies have not explored the mechanisms responsible for this effect, however, there is some evidence that volatile oils and constituents of the extracts may be responsible for the relief of some CNS disorders, but the effects on pain modulation seem to be the most exploited so far.
RESUMEN
Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS.