Opioid-based micro and nanoparticulate formulations: alternative approach on pain management.

CONTEXT: Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. OBJECTIVE: Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. METHODS: Papers available in 1995-2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. RESULTS: Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. CONCLUSION: Particulate formulations can significantly increase both potency and safety profiles of opioids.

Immunomodulatory and antibacterial activities of extracts from Rutaceae species / Atividade imunomoduladora e antibacteriana de extratos de espécies da família Rutaceae

Rutaceae is a taxon with species very well distributed in Brazilian semi-arid area, commonly used in folk medicine. Species from this genus have diverse biological activity described in literature. In this work, immunomodulatory and bactericidal activity are described for chloroform and ethyl acetate extracts of three of them (Esenbeckia grandiflora Mart., Pilocarpus spicatus A.St.-Hil. and Galipea simplicifolia Schult.). Initially all the samples had their cytotoxicity evaluated, aiming to determine the LC50. The immunomodulatory potential was evaluated in cultures of murine splenocytes stimulated or not with concanavalin A and in a mixed lymphocyte reaction (MLR) using splenocytes from BALB/c (H-2d) mice immunized with splenocytes from C57Bl/6 (H-2b) mice. Four samples had higher values of lymphoproliferation inhibition in concanavalin A-stimulated cultures and were evaluated in MLR. The antibacterial activity of extracts was also evaluated and the minimal inhibitory concentrations (MIC) for two active samples were 1.0 and 5.0 mg/ml for extracts from Esenbeckia grandiflora Mart. and Galipea simplicifolia Schult., respectively. Thus, our results reinforce data of literature relating biological activity for many species of the Rutaceae family and encourage studies with these species aiming to discover active compounds, candidates to new medicines.

A família Rutaceae apresenta espécies vegetais muito bem distribuídas no Semi-Árido Brasileiro e comumente usadas em medicina popular. Espécies dessa família tem diversas atividades biológicas descritas na literatura. Neste trabalho, atividades imunomoduladora e bactericida são descritas para o extrato acetato de etila e clorofórmico de três espécies da família (Esenbeckia grandiflora Mart., Pilocarpus spicatus A.St.-Hil. e Galipea simplicifolia Schult.). Todas as amostras foram inicialmente avaliadas quanto à sua citotoxicidade, com objetivo de determinar a LC50. O potencial imunomodulador foi avaliado em culturas de esplenócitos murinos estimulados ou não com concanavalina A e também em reação mista linfocitária (RML), usando também esplenócitos de camundongos BALB/c (H-2d) imunizados com esplenócitos de camundongos C57Bl/6 (H-2b). Quatro amostras tiveram os mais elevados valores percentuais de inibição da proliferação de linfócitos ativados pela concanavalina A e foram avaliados em RML. A atividade antibacteriana dos extratos foi também avaliada e a concentração mínima inibitória (CMI) para duas amostras ativas foi de 1.0 e 5.0 mg/mL, respectivamente para as espécies Esenbeckia grandiflora Mart. and Galipea simplicifolia Schult. Assim, os dados aqui apresentados reforçam informações da literatura científica relacionados à atividade biológica para muitas espécies da família Rutaceae e incentivam outros estudos com estas visando descobrir substâncias ativas, potenciais candidatas a novos fármacos.

Validation of a high-performance liquid chromatography method for the determination of (-)-alpha-bisabolol from particulate systems.

A reversed-phase high performance liquid chromatography method has been developed and validated for determination and quantitation of the natural sesquiterpene (-)-alpha-bisabolol. Furthermore the application of the method was done by characterization of chitosan milispheres and liposomes entrapping Zanthoxylum tingoassuiba essential oil, which contains appreciable amount of (-)-alpha-bisabolol. A reversed-phase C(18) column and gradient elution was used with the mobile phase composed of (A) acetonitrile-water-phosphoric acid (19:80:1) and (B) acetonitrile. The eluent was pumped at a flow rate of 0.8 mL/min with UV detection at 200 nm. In the range 0.02-0.64 mg/mL the assay showed good linearity (R(2 )= 0.9999) and specificity for successful identification and quantitation of (-)-alpha-bisabolol in the essential oil without interfering peaks. The method also showed good reproducibility, demonstrating inter-day and intra-day precision based on relative standard deviation values (up to 3.03%), accuracy (mean recovery of 100.69% +/- 1.05%) and low values of detection and quantitation limits (0.0005 and 0.0016 mg/mL, respectively). The method was also robust for showing a recovery of 98.81% under a change of solvent in standard solutions. The suitability of the method was demonstrated by the successful determination of association efficiency of the (-)-alpha-bisabolol in chitosan milispheres and liposomes.