Oil-in-microgel strategy for enzymatic-triggered release of hydrophobic drugs.

Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets. The procedure is used for the encapsulation and controlled release of progesterone. Degradability and encapsulation/release studies in PBS buffer at 37°C in presence of different concentrations of hyaluronidase are performed. It is demonstrated that enzymatic degradation can be used to trigger the release of progesterone from microgels. This method provides precise control of the release system and can be applied for the encapsulation and controlled release of different types of hydrophobic drugs.

N-butyl-[1-(4-methoxy)phenyl-9H-ß-carboline]-3-carboxamide prevents cytokinesis in Leishmania amazonensis.

Leishmaniasis, a complex of diseases caused by protozoa of the genus Leishmania, is endemic in 98 countries, affecting approximately 12 million people worldwide. Current treatments for leishmaniasis have many disadvantages, such as toxicity, high costs, and prolonged treatment, making the development of new treatment alternatives highly relevant. Several studies have verified the antileishmanial activity of ß-carboline compounds. In the present study, we investigated the in vitro antileishmanial activity of N-butyl-[1-(4-methoxy)phenyl-9H-ß-carboline]-3-carboxamide (ß-CB) against Leishmania amazonensis. The compound was active against promastigote, axenic amastigote, and intracellular amastigote forms of L. amazonensis, exhibiting high selectivity for the parasite. Moreover, ß-CB did not exhibit hemolytic or mutagenic potential. Promastigotes treated with the alkaloid presented rounding of the body cell, cell membrane projections, an increase in the number of promastigotes presenting two flagella, and parasites of abnormal phenotype, with three or more flagella and/or nuclei. Furthermore, we observed an increase in the subpopulation of cells in the G2/M stage of the cell cycle. Altogether, these results suggest that ß-CB likely prevents cytokinesis, although it does not interfere with the duplication of cell structures. We also verified an increase in O2(·-) production and the accumulation of lipid storage bodies. Cell membrane integrity was maintained, in addition to the absence of phosphatidylserine externalization, DNA fragmentation, and autophagosomes. Although the possibility of an apoptotic process cannot be discarded, ß-CB likely exerts its antileishmanial activity through a cytostatic effect, thus preventing cellular proliferation.

Rheological properties of calcium carbonate self-setting injectable paste.

With the development of minimally invasive surgical techniques, there is growing interest in the research and development of injectable biomaterials with controlled rheological properties. In this context, the rheological properties and injectability characteristics of an original CaCO(3) self-setting paste have been investigated. Two complementary rheometrical procedures have been established using a controlled stress rheometer to follow the structure build-up at rest or during gentle mixing and/or handling on the one hand, and the likely shear-induced breakdown of this structure at 25 or 35 degrees Celsius on the other. The data obtained clearly show the influence of temperature on the development of a cement microstructure during setting, in all cases leading to a microporous cement made of an entangled network of aragonite-CaCO(3) needle-like crystals. Linear viscoelastic measurements arriving from an oscillatory shear at low deformation showed a progressive increase in the viscous modulus (G'') during paste setting, which is enhanced by an increase in temperature. In addition, steady shear measurements revealed the shear-thinning behaviour of this self-setting paste over an extended period after paste preparation and its ability to re-build through progressive paste setting at rest. The shear-thinning behaviour of this self-setting system was confirmed using the injectability system and a procedure we designed. The force needed to extrude a homogeneous and continuous column of paste decreases strongly upon injection and reaches a weight level to apply on the syringe piston around 2.5 kg, revealing the ease of injection of this CaCO(3) self-setting paste.

Synthesis and evaluation of the mucoadhesivity of a CD-chitosan derivative.

Combining mucoadhesive characteristics of a biodegradable polymer such as chitosan with the potential to enhance drug release by increasing the solubility of poorly water-soluble drugs has great potential for pharmaceutical technology and drug delivery design. Polymeric delivery systems have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins (CD) offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs altering their physicochemical properties. In the continuing challenge to improve the properties of delivery systems, this paper focuses on the modification of chitosan by introducing beta-cyclodextrin and to test the mucoadhesive strength and inclusion properties of this synthesised cyclodextrin-polymer. beta-Cyclodextrin was successfully grafted onto a chitosan chain polymer with a cyclodextrin grafting yield of 7% and a CD-chitosan yield of 85%. Although the complexation of (+)-catechin by the grafted beta-CD was found to be about five times weaker than that by the beta-CD monoaldehyde and natural beta-CD, the inclusion properties of the chitosan-CD remain promising. The mucoadhesive properties of chitosan-CD were compared to that of pectin (reference) and the parent chitosan with the use of a tensile separation test. The chitosan-CD showed mucoadhesive strengths of 12% stronger than pectin, but 13.5% weaker than the parent chitosan. The synthesised chitosan-CD-polymer exhibits characteristics of a possible mucoadhesive drug delivery system with some inclusion properties from beta-cyclodextrin.