RESUMO
Introduction: Cannabidiol (CBD), the nonintoxicating constituent of cannabis, is largely employed for pharmaceutical and cosmetic purposes. CBD can be extracted from the plant or chemically synthesized. Impurities of psychotropic cannabinoids Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-THC have been found in extracted CBD, thus hypothesizing a possible contamination from the plant. Materials and Methods: In this study, synthetic and extracted CBD samples were analyzed by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry and the parameters that can be responsible of the conversion of CBD into THC were evaluated by an accelerated stability test. Results: In synthetic and extracted CBD no trace of THC species was detected. In contrast, CBD samples stored in the dark at room temperature on the benchtop for 3 months showed the presence of such impurities. Experiments carried out under inert atmosphere in the absence of humidity or carbon dioxide led to no trace of THC over time even at high temperature. Conclusions: The results suggested that the copresence of carbon dioxide and water from the air could be the key for creating the acidic environment responsible for the cyclization of CBD. These findings suggest that it might be appropriate to review the storage conditions indicated on the label of commercially available CBD.
Assuntos
Canabidiol/química , Dronabinol/análise , Dronabinol/química , Canabidiol/síntese química , Canabidiol/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Dronabinol/análogos & derivados , Contaminação de Medicamentos , Espectrometria de Massas , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
The chemical analysis of cannabis potency involves the qualitative and quantitative determination of the main phytocannabinoids: Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), etc. Although it might appear as a trivial analysis, it is rather a tricky task. Phytocannabinoids are present mostly as carboxylated species at the aromatic ring of the resorcinyl moiety. Their decarboxylation caused by heat leads to a greater analytical variability due to both reaction kinetics and possible decomposition. Moreover, the instability of cannabinoids and the variability in the sample preparation, extraction, and analysis, as well as the presence of isomeric forms of cannabinoids, complicates the scenario. A critical evaluation of the different analytical methods proposed in the literature points out that each of them has inherent limitations. The present review outlines all the possible pitfalls that can be encountered during the analysis of these compounds and aims to be a valuable help for the analytical chemist. Graphical abstract.
Assuntos
Canabinoides/análise , Cannabis/química , Técnicas de Química Analítica/métodos , Inflorescência/química , Extratos Vegetais/química , Cromatografia Gasosa/métodos , Cromatografia Líquida/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Hemp seed oil from Cannabis sativa L. is a very rich natural source of important nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes and cannabinoids, which contribute to the overall beneficial effects of the oil. Hence, it is important to have an analytical method for the determination of these components in commercial samples. At the same time, it is also important to assess the safety of the product in terms of amount of any psychoactive cannabinoid present therein. This work presents the development and validation of a highly sensitive, selective and rapid HPLC-UV method for the qualitative and quantitative determination of the main cannabinoids, namely cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidivarin (CBDV), present in 13 commercial hemp seed oils. Moreover, since decomposition of cannabinoid acids generally occurs with light, air and heat, decarboxylation studies of the most abundant acid (CBDA) were carried out in both open and closed reactor and the kinetics parameters were evaluated at different temperatures in order to evaluate the stability of hemp seed oil in different storage conditions.
Assuntos
Canabinoides/farmacocinética , Cannabis/química , Cromatografia Líquida de Alta Pressão/métodos , Óleos de Plantas/química , Espectrofotometria Ultravioleta/métodos , Canabinoides/análise , Canabinoides/química , Cromatografia Líquida de Alta Pressão/instrumentação , Descarboxilação , Inocuidade dos Alimentos/métodos , Armazenamento de Alimentos , Psicotrópicos/análise , Psicotrópicos/química , Sementes/química , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta/instrumentação , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodosRESUMO
A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson's and Alzheimer's disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.
Assuntos
Encéfalo/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/administração & dosagem , Portadores de Fármacos , Nanopartículas , Zinco/administração & dosagem , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Cátions Bivalentes/administração & dosagem , Cátions Bivalentes/farmacocinética , Cátions Bivalentes/toxicidade , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Avaliação Pré-Clínica de Medicamentos , Glicopeptídeos/química , Glicopeptídeos/toxicidade , Imuno-Histoquímica , Ácido Láctico/química , Ácido Láctico/toxicidade , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/química , Nanopartículas/toxicidade , Ácido Poliglicólico/química , Ácido Poliglicólico/toxicidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Zinco/farmacocinética , Zinco/toxicidadeRESUMO
Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 ± 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.
Assuntos
Aminoácidos/administração & dosagem , Lesões Encefálicas/tratamento farmacológico , Ácido Láctico , Nanopartículas , Fármacos Neuroprotetores/administração & dosagem , Ácido Poliglicólico , Aminoácidos/sangue , Aminoácidos/química , Aminoácidos/uso terapêutico , Animais , Barreira Hematoencefálica , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Preparações de Ação Retardada , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Emulsões , Liofilização , Interações Hidrofóbicas e Hidrofílicas , Masculino , Microscopia Eletrônica de Varredura , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Concentração Osmolar , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Trealose/químicaRESUMO
Cloricromene (AD6), an anti-ischemic drug, is rapidly metabolised into a stable and active metabolite (cloricromene acid, AD6-acid) poorly soluble in water and less lipophilic than cloricromene. The aim of this study was to evaluate which of the two forms has more possibility to be efficiently encapsulated in nanoparticles based on poly(D,L-lactide) and prepared using the nanoprecipitation method. Increasing the theoretical loading of AD6, an increase in drug actual loading and in the mean particle size occurred, while no formation of nanoparticles was observed when the highest theoretical loading (50 mg) was employed. Changing the pH of the aqueous phase the drug content dramatically increased. However, at a pH value of 11 a more rapid hydrolysis of AD6 occurred. When AD6-acid was embedded in the nanoparticles, suitable results concerning both drug content and encapsulation efficiency were achieved. A good control in the release of AD6 from the AD6-loaded nanoparticles was observed while the liberation of AD6-acid from the AD6-acid-loaded nanoparticles was faster than the dissolution of the AD6-acid free. These results confirm that the most easy encapsulable form in nanoparticles is AD6-acid probably owing to its poor water solubility. Further studies will be carried out in order to evaluate if the increase in the liberation of AD6-acid by nanoencapsulation may have outcomes in its bioavaibility in vivo.
Assuntos
Cromonar/análogos & derivados , Lipídeos/química , Nanotecnologia/métodos , Poliésteres/química , Água/química , Cromonar/química , Cromonar/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Concentração de Íons de Hidrogênio , Lipídeos/farmacocinética , Microscopia Eletrônica de Varredura , Poliésteres/farmacocinética , Solubilidade/efeitos dos fármacosRESUMO
The present study is a preliminary exploration of the affinity between a carboxylic model drug, the nonsteroidal antiinflammatory agent ibuprofen (IBU) and Eudragit RL100 (RL) polymer. Due to the presence of a variable amount of quaternary ammonium groups in this matrix, physical and chemical interaction with the carboxylic drug can occur, which reinforces its scant mechanical dispersion in the polymer network and can ultimately affect its release profile in vitro and in vivo. To study these aspects, IBU was mixed at increasing weight ratios and in different chemical forms (free acid, sodium salt, and n-butyl ester), to investigate further the role of the carboxylic group in the interaction with the RL polymer. Therefore, IBU-RL solid dispersions (coevaporates) were obtained and fully characterized in the solid state through spectroscopic, calorimetric, and x-ray diffractometric analyses. The in vitro release pattern of the drug, in the different chemical states, was studied for the coevaporates, compared with drug-RL physical mixtures, along with drug adsorption profiles from aqueous solutions on the surface of the polymer granules.