RESUMO
Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed.
Assuntos
Lipídeos/química , Nanopartículas/química , Retinoides/administração & dosagem , Retinoides/química , Administração Cutânea , Animais , Humanos , Pele/metabolismo , Absorção CutâneaRESUMO
Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated.
Assuntos
Epigenômica , Neoplasias/genética , Neoplasias/prevenção & controle , Ciências da Nutrição , Medicina Preventiva/métodos , Animais , Anticarcinógenos/uso terapêutico , Butiratos/química , Metilação de DNA , Dieta , Epigênese Genética , Ácidos Graxos , Alimentos , Histonas/metabolismo , Humanos , Modelos Biológicos , Neoplasias/metabolismo , Polifenóis/química , Retinoides/química , Selênio/químicaRESUMO
Retinoic acid and insect juvenile hormone (JH) are structurally related terpenoids which are widespread in nature and are involved in many biological events such as morphogenesis, embryogenesis and cellular differentiation. Here, we investigated the effects of the retinoids 9-cis retinoic acid (9cisRA), all trans retinol (atROH), all trans retinoic acid (atRA) and the juvenoids methoprene (Met) and JH injection on moult and on phenoloxidase activity in the blood-sucking insect Rhodnius prolixus. Overall, we observed that injection of retinoids or juvenoids (120 pmols) in the hemocoel of 4th instar nymphs reduced the percentage of insects which appeared normal in morphology upon moult. Noteworthy, insects exposed to 9cisRA or JH underwent profound morphological changes upon moult, generating abnormal 5th instar nymphs and also markedly increased the death of insects during the moulting process. In addition, reduction in the percentage of insects that moult without any morphological alteration, induced by retinoids or juvenoids treatment, was negatively correlated with insects that both display abnormal moult and those that die during moult. Hemolymphatic phenoloxidase activity in adult male insects injected with 9cisRA, Met and JH were significantly reduced after a bacterial challenge. Together, these results indicate that not only juvenoids but also retinoids play an important role on morphogenesis and on immune response in R. prolixus, suggesting that the molecular mechanisms involved in these events recognize the terpenoid backbone as an important structural determinant in insects.
Assuntos
Hormônios Juvenis/farmacologia , Metoprene/farmacologia , Muda/efeitos dos fármacos , Monofenol Mono-Oxigenase/efeitos dos fármacos , Retinoides/farmacologia , Rhodnius/efeitos dos fármacos , Animais , Hormônios Juvenis/química , Metoprene/química , Monofenol Mono-Oxigenase/metabolismo , Retinoides/química , Rhodnius/enzimologia , Rhodnius/crescimento & desenvolvimentoRESUMO
The retinoic acid receptor (RAR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily. The ligand-binding domain contains the ligand-dependent activation function. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids involved in the treatment of various cancers and skin diseases. There is thus considerable interest in synthetic retinoids with isotype selectivity and reduced side effects. In this work we have focused on the retinoid acid receptor and three of its panagonists. We have carried out density functional geometry optimizations at the B3LYP/6-31G* level, computed two types of atomic charges and also electrostatic potentials. A docking program was used to investigate the interactions between the receptor and the three ligands. A theoretically more potent inhibitor, which was obtained by modifying one of the retinoic acids investigated, is proposed.