Diogo Matias

Phytosomes as Biocompatible Carriers of Natural Drugs

Natural products have been frequently used as sources of clinical useful pharmaceuticals. However, some intrinsic characteristics of the natural drugs have limited their use, namely their solubility and chemical stability in physiologic mediums. Innovative drug delivery systems may help overcome such limitations, thus providing more effective administration of natural products. Phytosome (Indena SPA, Italy) is one of the most exciting recent delivery technologies that improves the oral bioavailability of the phytopharmaceuticals by their inclusion in equimolar complexes with dietary phospholipids with vesicular shape in aqueous environments. The purpose of this review is to characterize the state of the art of the phytosome as drug delivery system of natural products, including a discussion of the natural drug-phospholipid complex interactions, mechanisms of oral and topical delivery, methods of preparation and phytosome recent applications and patents in the 2006-2016 period.

Plectranthus madagascariensis phytosomes: formulation optimization: Fitossomas de Plectranthus madagascariensis: otimização da formulação

Medicinal plants have been a reliable source of bioactive natural products with potential pharmaceutical applications. The delivery of those bioactive agents into nanosystems is considered a promising strategy for the optimization of their pharmacologic effects. This work describes the preparation of phytosomes containing a bioactive extract from Plectranthus madagascariensis and optimization of the preparation method. Different formulations and process parameters were studied. It was observed that smaller and more uniform particles were obtained using acetone as solvent, a reaction time of two hours, and the addition of 2.5% molar concentration of cholesterol. The optimally prepared phytosomes had a diameter of 191.3 ± 75.3 nm with a polydispersity index of 0.243 ± 0.18, and a spherical shape with amorphous appearance. These nanosystems were able to encapsulate 92.8% of the extract, as evaluated by HPLC, relative to 7α,6β-dihydroxyroyleanona, the main extract component. This study suggests a future application of those phytosomes in the delivery of bioactive agents with therapeutic interest.

Antimicrobial screening of Plectranthus madagascariensis and P. neochilus extracts Pesquisa da actividade antimicrobiana de extratos de Plectranthus madagascariensis e P. neochilus

Natural products are widely used as traditional medicines and are a common source of bioactive molecules for the treatment of bacterial infections. In particular, some plants of the genus Plectranthus (Lamiaceae) have demonstrated several applications, including the treatment of various infections. In this work, aqueous, acetonic and methanolic extracts of P. madagascariensis and P. neochilus were prepared using several extraction methods (infusion, decoction, maceration, microwave- and ultrasoundassisted and supercritical fluids). All extracts were screened for their antimicrobial activity against Gram positive bacteria (Enterococcus faecalis, Staphylococcus aureus, Bacillus subtilis and Mycobacterium smegmatis) and Gram negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli) and two yeast (Candida albicans and Saccharomyces cerevisiae) strains. The P. madagascariensis acetonic extracts obtained using ultrasound and maceration methods and P. neochilus acetonic extract obtained by ultrasound technique showed activity against the five tested Gram positive bacteria (5‒24 mm of inhibition zone using the well diffusion test). The antimicrobial activity was further evaluated by the microdilution method (MIC values were between 250‒0.49 μg/mL) and the bioautography assay against S. aureus. The P. madagascariensis ultrasound acetonic extract was the most active extract against all the tested Gram positive bacteria (MIC values ranged between 31.25 - 0.49 μg/mL). It was also active against resistant MRSA and VRE strains (MIC values ranged between 31.25-0.98 μg/mL). The S. aureus bioautography assay showed that the more polar compounds were the responsible for the antimicrobial activity.

Optimization of the encapsulation efficiency of a novel oral insulin delivery nanosystem: Optimização da eficiência de encapsulaçãode um novo nanosistema para a administração oral de insulina

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. The oral delivery of insulin remains a challenge because of its limited absorption. The main goal of this study was to produce stable nanoparticles with high loads of insulin for further in vivo testing. Poli(lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer, revealed to be a good presupposition for this approach. Nanoparticles were produced through a multiple emulsion method and the encapsulation efficiency was accessed by a HPLC method. Monodispersed nanoparticles were produced and the insulin EE were improved from 30 % to 65 %, controlling parameters such as the stirring speed rate, volume of external phase, pH range, type of insulin, type of surfactant and polymer concentrations. The nanoparticle size was 398.6 nm with a polydispersivity index of 0.19. The presence of a salt concentration between 20 g L-1 and 50 g L-1 and the type of insulin decreased the size of nanoparticles. Bioactivity assessment after the encapsulation process and full characterization of physical-chemical interactions between all species is now required.