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Biodegradable polyesters, such as the poly(lactic-co-glycolic acid) (PLGA), have been extensively used as a polymer matrix for entrapping a variety of active compounds. In this study, the physicochemical phenomena that control the mass transport mechanism of hydrophilic compounds released from PLGA microspheres were identified. This study aims to produce and characterize PLGA microspheres loaded with metformin hydrochloride (MH) and perform a case study using the literature data of PLGA microspheres loaded with fluorescein isothiocyanate-dextran (FITC-dextran). The MH is a low molecular weight compound that was easily and rapidly transported by diffusion mechanism through the microsphere pores. The FITC-dextran, as a high molecular weight compound, depended on the mechanism of polymer erosion and mesopore formation, with 18 days of duration, before its release by diffusion mass transfer. Values of the effective diffusion coefficient of MH and FITC-dextran, both in PLGA, were 2.4 x 10-13 and 5.3 x 10-18 m2 s-1, respectively, with a difference of five orders of magnitude attributed to the molecular weight of these hydrophilic compounds and the main mass transport that governed their release. This study provides important insights into the mechanisms of mass transfer and their correlation with the physicochemical properties of both hydrophilic compounds and the PLGA matrix, contributing to the development of biodegradable controlled delivery systems for a variety of applications in chemical, biotechnological, and pharmaceutical industries. Los poliésteres biodegradables, como el poli(ácido láctico-co-glicólico) (PLGA), se han utilizado ampliamente como matriz polimérica para encapsular una variedad de compuestos activos. En este estudio, se identificaron los fenómenos fisicoquímicos que controlan el mecanismo de transporte de masa de los compuestos hidrofílicos liberados de microesferas de PLGA. Este estudio tiene como objetivo producir y caracterizar microesferas de PLGA cargadas con clorhidrato de metformina (CM) y realizar un estudio de caso utilizando datos de la literatura de microesferas de PLGA cargadas con isotiocianato de fluoresceína (FITC)-dextrano. El CM es un compuesto de baja masa molecular que fue transportado rápidamente por el mecanismo de difusión a través de los poros de la microesfera. El FITC-dextrano, como compuesto de alta masa molecular, dependió del mecanismo de erosión del polímero y de la formación de mesoporos, durante 18 días, antes de su liberación por transferencia de masa por difusión. Los valores del coeficiente de difusión efectivo del CM y del FITC-dextrano, ambos en PLGA, fueron iguales a 2,4 x 10-13 y 5,3 x 10-18 m2 s-1, respectivamente, con una diferencia de cinco órdenes de magnitud atribuida a las diferentes masas moleculares de estos compuestos hidrofílicos y al principal mecanismo de transporte de masa durante la liberación. Este estudio proporciona importantes conocimientos sobre los mecanismos de transferencia de masa y su correlación con las propiedades fisicoquímicas tanto de los compuestos hidrofílicos como de la matriz de PLGA, contribuyendo al desarrollo de sistemas biodegradables de liberación controlada para diversas aplicaciones en la industria química, biotecnológica y farmacéutica. Poliésteres biodegradáveis, como o poli(ácido láctico-co-glicólico) (PLGA), têm sido amplamente utilizados como matriz polimérica para encapsular uma variedade de compostos ativos. Neste estudo, os fenômenos físico-químicos que controlam o mecanismo de transporte de massa de compostos hidrofílicos liberados de microesferas PLGA foram identificados. Este estudo visa produzir e caracterizar microesferas de PLGA carregadas com cloridrato de metformina (CM) e realizar um estudo de caso utilizando dados da literatura de microesferas de PLGA carregadas com isotiocianato de fluoresceína (FITC)-dextrano. O CM é um composto de baixa massa molecular que foi rapidamente transportado por mecanismo difusivo através dos poros da microesfera. O FITC-dextrano, por ser um composto de alta massa molecular, dependeu do mecanismo de erosão do polímero e formação dos mesoporos, com 18 dias de duração, antes da sua liberação por transferência de massa por difusão. Os valores do coeficiente de difusão efetivo do CM e do FITC-dextrano, ambos em PLGA, foram iguais a 2,4 x 10-13 e 5,3 x 10-18 m2 s-1, respectivamente, com uma diferença de cinco ordens de grandeza atribuídas às diferentes massas moleculares desses compostos hidrofílicos e ao principal mecanismo de transporte de massa durante a liberação. Este estudo fornece informações importantes sobre os mecanismos de transferência de massa e sua correlação com as propriedades físico-químicas tanto dos compostos hidrofílicos quanto da matriz de PLGA, contribuindo com o desenvolvimento de sistemas de liberação controlada biodegradáveis para uma variedade de aplicações nas indústrias químicas, biotecnológicas e farmacêuticas.

The high biocompatibility, flexible nature, and adhesive effect of hydrogels are attractive properties for their application as controlled drug-delivery systems. On the other hand, hydrogels in the swollen state are characterized by a low mechanical strength, which represents an important limitation for their biomedical application. The incorporation of nanoparticles in hydrogels is a promising alternative to overcome this limitation, by which multiresponsive hydrogels with improved mechanical, physical, and biological properties may be obtained. The resulting chemical interactions between nanoparticles and the polymeric network can provide hydrogel nanocomposite systems that are characterized by a unique network structure. These systems may be defined as hydrated polymeric networks, physically or covalently crosslinked with one another and/or with nanoparticles. A wide range of nanoparticles, such as carbon nanotubes and ceramic, metal, polymeric, and liposomal nanoparticles, have been incorporated in hydrogels to obtain drug-delivery systems with superior properties and tailored functionality. In this chapter, general aspects and advances in the development, functionalization, characterization, and application of hydrogel nanocomposites are presented, focusing on drug-delivery systems.

We report on the preparation and characterization of nanocomposite chitosan hydrogels with embedded poly (lactic-co-glycolic acid) (PLGA) nanoparticles employed for encapsulation of an enriched flavonoid fraction of Cecropia glaziovii Snethl. As a first step, the experimental conditions to obtain homogeneous chitosan hydrogels at 37 °C through gelation with NaHCO were optimized. Then, nanocomposite chitosan hydrogels were prepared through direct incorporation of nanoparticlesat different concentrations ranging from 1 to 10% w/w to gelling aqueous chitosan solutions. The resulting hydrogels were characterized through Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), oscillatory rheological experiments and cytotoxicity tests. FT-IR spectra confirmed the PLGA nanoparticles presence within the chitosan matrix through the absorption peak located at 1750 cm. The presence of the PLGA nanoparticles decreased the thermal stability of the nanocomposite chitosan hydrogels compared to the pure chitosan hydrogel. SEM images allowed observing porous matrixes where nanoparticles appeared to be homogeneously dispersed. The elastic moduli found for nanocomposite chitosan hydrogels varied with the PLGA nanoparticles concentration with a maximum at 3% nanoparticles concentration. Cytotoxicity tests revealed that after 48 h, neither thepure hydrogel nor the nanocomposite chitosan hydrogels with 10% nanoparticles concentration showed toxicity on VERO cells., Talitha Caldas dos Santos thanks Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the graduate scholarship. Financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) (project MAT 2014-53437-C2-1P) is also acknowledged. The authors thank Izabella Thaís da Silva for support in the cytotoxic assays.

In this study, the standardized dry extract of C. glaziovii (SDE) provided a significant vasorelaxant effect after contractions induced by phenylephrine in rat aortic rings in an endothelium-dependent manner, confirming that endothelial factors are needed to stimulate this response. A vasorelaxation close to that of acetylcholine was achieved, justifying the development of new formulations for this plant material. In this context, microparticles were selected to encapsulate SDE and the double emulsion technique was considered because of the hydrophilic nature of plant material. Two experimental designs were applied. Firstly, the effect of formulation parameters on particle size, size distribution and encapsulation efficiency (EE) was evaluated. As low EE was achieved, the effect of the osmotic pressure of the external phase was evaluated in a second experimental design. The presence of the osmotic agent (NaCl) impacted positively on the EE and slower in vitro release profile was obtained, which is desired in controlled release systems. The formation of denser and less porous particle surface, which was identified by SEM analysis, contributes to explain these findings. Microstructures showed to be a promising delivery system for the C. glaziovii SDE considering that a sustained release was achieved.

Oral bioavailability of C-glycosyl flavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) is limited due to its chemical complexity. The purpose of this study is the prospective evaluation of chitosan buccal films impregnated with EFF-Cg-loaded nanospheres as a drug delivery system for labial herpes treatment or for buccal administration. EFF-Cg-loaded PLGA nanospheres were prepared by double emulsion solvent evaporation technique. Nanoparticles were embedded into buccoadhesive chitosan films in different concentrations in order to obtain nanocomposite films. Films were characterized in term of morphology, mechanical properties and water absorption test. Furthermore a cytotoxicity assay was analyzed to evaluate the biocompatibility of systems. The results obtained from these analyses revealed that nanocomposite films present transparent appearance in all composition and Scanning Electron Microscopy (SEM) images show a continuous and compact section structure. Compared to the control film, mechanical responses of nanocomposites presented lower tensile strength values and no significant effect on the elongation at break. Dynamic Mechanical Analysis (DMA) tests indicated that increasing of NP concentration caused decreased stiffness and an increased of glass transition temperature values. Direct cytotoxicity test shows that nanoparticles and chitosan films not induce cytotoxic effect. Given the promising results, the study concludes that the developed buccal film impregnated with EFF-Cg-loaded nanospheres could be a promising approach for effective delivery of EFF-Cg., Talitha Caldas dos Santos thanks Coordenac¸ ão deAperfeic¸oamento de Pessoal de Nível Superior (CAPES) forthe graduate scholarship. Financial support from the SpanishMinisterio de Economía y Competitividad (MINECO) (project MAT2014-53437-C2-1P) is also acknowledged.

In this work is reported a novel and promising approach for the preparation of C -glycosylflavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) loaded PLGA nanoparticles (NP) with antiherpes properties. The purpose of this study was to evaluate and to compare the effect of two nonionic surfactants (poloxamer 188 (PLU) and polyvinyl alcohol (PVA)), and also an emulsion stabilized by solid particles of cellulose nanocrystal (CNC) in place of surfactants. The characterization of these nanoparticles was in terms of size, polydispersity index, zeta potential, morphology, thermogravimetric analysis (TGA), loading capacity and percent yield. Since TGA analysis revealed thermo stability especially for NP-PLU, this formulation was selected for the evaluation of drug release profile, cytotoxicity and antiherpes activity. The drug delivery profile demonstrated a sustained release through the polymer structure and a significant reduction of the polymer molecular weight at 21-day period. The cytotoxicity of these nanoparticles was determined on Vero cells, and the selected formulation did not exhibit cytotoxicity even at the highest tested concentration. The results demonstrated a potential antiherpetic effect of the EFF-Cg loaded NP at 48 h of testing. In summary, EFF-Cg loaded NP exhibited a promising system for the effective drug delivery in the treatment of herpes infections.

Studies employing

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties.

Eudragit® RS100 microspheres of two chalcones were prepared by solvent evaporation technique. A simple and rapid high-performance liquid chromatography (HPLC) method was developed and validated to determine the encapsulation efficiency, drug loading and release profiles of these chalcones in a microparticulate system. The mean EE values for the two chalcones-loaded microparticles were 98.8 ± 1.3% and 99.5 ± 0.9%. Scanning electron microscope (SEM) studies showed that one chalcone-loaded microspheres are spherical and smooth appearance whereas the other chalcone-loaded microspheres showed irregular particles and a rough surface. The analysis of the second chalcone by thermogravimetric analysis (TGA) showed a higher thermal stability compared to the first chalcone. Drug release profiles were determined at pH 7.4 phosphate buffered saline (100 mmol L-1) with sodium lauryl sulfate (0.5%). The systems prepared with Eudragit® showed 78 and 95% of the two chalcones were released after 24 hours. The experimental results indicated that the prepared polymeric microspheres may be useful for potential applications.

The effects of different parameters, including ethanol concentration, time of drug:solvent contact, temperature and the presence of a preservative, on chlorogenic acid (CGA) and caffeic acid (CFA) yields in Cecropia glaziovii Sneth extracts were investigated using an experimental design. In order to quantify the phenolic acids in these extracts a high-performance liquid chromatography–diode array detection (HPLC–DAD) method was developed and validated. Extracts with 80% ethanol presented a higher CGA content, but low amounts of CFA. Extracts with 20% ethanol showed a higher CFA concentration, but a sharp reduction in CGA extraction yield. The presence of a preservative, under the same extraction conditions, resulted in a slight difference or no difference in the CGA and CFA extraction yields. When the temperature was controlled at refrigerator or room temperature, a slight alteration in the concentrations of the phenolics studied was observed. The present approach can be applied in order to determine the optimum conditions for the preparation of C. glaziovii Sneth extracts based on CGA or CFA extraction yield as a chemical marker.

The aim of this study is to investigate the effect of Cecropia glaziovii Snethl, Urticaceae, extracts on the oral glucose tolerance curve, on glycemia in alloxan-induced diabetic rats and vasorelaxant effect after the extraction process, and to standardize the extractive solutions. The effects of the process variables and their interactions were calculated in relation to dry residue, pH, total phenolic results and chemical marker content. Furthermore, the effect of the extracts (400 mg/kg), chlorogenic (2 or 15 mg/kg) and caffeic acids (2 mg/kg) were investigated on the oral glucose tolerance curve and on glycemia in alloxan-induced diabetic rats. Oral administration of ethanol extracts 4d20 and 8d20 significantly improved glucose tolerance in the hyperglycemic rats. Chlorogenic and caffeic acids, as well as the association of the compounds were able to significantly reduce glycemia after oral gavage treatments. On the other hand, the aqueous extracts did not alter the glycemia. The aqueous extracts (8020 and 9030) and only the higher dose of chlorogenic acid presented a significant effect on serum glucose lowering in diabetic rats. Additionally, the IC50 reveals that the ethanol extracts presented more potent vasodilator effects than the aqueous extracts in aortic rings. This study shows that C. glaziovii standardized extracts exhibits antihyperglycemic action, is able to improve glucose tolerance and has a potent vascular relaxing effect. These results are probably linked to concentrations of the main phenolic compounds of the extracts. Keywords: Cecropia glaziovii, Decoction, Maceration, Total phenolic, Antihyperglycemic activity, Vasorelaxant activity