Carlos Peniche Covas

Self-assembled nanoparticles of modified-chitosan conjugates for the sustained release of dl-α-tocopherol

Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254-496 nm mean diameters and dl-α-tocopherol contents between 27 and 39% (w/w). The particles appeared as 40-75 nm almost spherical nanoparticles when studied by scanning and transmission electron microscopy upon drying. Drug linking to chitosan matrix was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning calorimetry and wide-angle X-ray diffraction. In vitro tocopherol release studies performed in water at acid pH indicated a drug release dependence on drug content, hydrated particle sizes and employed chitosan derivative. Almost constant release rates were observed the first 7h. The obtained nanoparticles exhibited radical scavenging activity in DPPH essay. The potential of these nanoparticles was also demonstrated by the enhancement of HMVEC cell proliferation.

N,O6-partially acetylated chitosan nanoparticles hydrophobically-modified for controlled release of steroids and vitamin E

Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning calorimetry and wide-angle X-ray diffraction. These conjugates formed self-assembled nanoparticles in aqueous solution with particle sizes ranging from 197 to 358 nm and drug contents between 11.8 and 56.4% (w/w). Spherical 30-60 nm nanoparticles were observed by scanning electron microscopy and transmission electron microscopy upon drying. In vitro release studies performed at acid pH indicated a drug release dependence on substitution degree and particle sizes. Almost constant release rates were observed during the first 6-8h. Brassinosteroids-modified nanoparticles showed good agrochemical activity in radish seeds bioassay at 10(-1) to 10(-4) mg mL(-1). Tocopheryl-modified nanoparticles exhibited radical scavenging activity in DPPH test.

Thermal properties, nanoscopic structure and swelling behavior of chitosan/(ureasil–polyethylene oxide hybrid) blends

In this work, the effect of chitosan blending on the thermal properties, nanoscopic structure and swelling behavior of ureasil–polyethylene oxide (U-PEO) hybrid materials was examined. Materials were prepared by the sol–gel route using acid catalysts, and the effect of acid (hydrochloric or acetic acid) was also examined. Differential scanning calorimetry results showed that chitosan addition did not provoke appreciable changes in the thermal behavior of the U-PEO. Thermogravimetric curves did not show changes in thermal stability resulting from chitosan blending but were depended on the type of acid catalyst. Small-angle X-ray scattering and nuclear magnetic resonance spectroscopy techniques were used for studying nanoscopic and inner structures, showing the existence of two structural levels and differences in polycondensation degrees. All samples presented fast water uptake with the same initial swelling rate and with a non-Fickian or anomalous transport mechanism. Swelling degree was higher in hybrids prepared with HCl, which possessed less branched siloxane cross-link nodes species, therefore lower polycondensation degree. Also, the magnitude of swelling decreased for hybrids blended with chitosan, which provides a means of tailoring the water uptake by the ureasil–PEO hybrid and to potentiate the control of the release profile of drugs incorporated in these materials.

Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals

Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

Hydrophobically-modified Chitosan Microspheres for Release of Diosgenin

Chitosan microspheres (CS) prepared by water-in-oil emulsion/glutaraldehyde cross-linking-evaporation and simple coacervation/cross-linking with sodium tripolyphosphate were covalently linked to diosgenin hemiesters. The diosgenin content found using elemental analysis was ca. 6 to 42 wt-% and it showed dependence on the type of diosgenin hemiesters and on the method of preparation of the CS microspheres. Fourier transform infrared spectroscopy confirmed the hydrophobic functionalization of CS with the diosgenin hemiesters by amide bond formation. The effect of CS modification with diosgenin on the thermal properties was also studied using differential scanning calorimetry. Microsphere sizes determined using optical microscopy ranged from 60 to 700 um, while scanning electron microscopy depicted morphology dependent on the selected method to obtain CS microspheres. In vitro release studies performed in aqueous medium indicated a drug release dependence on the diosgenin hemiester linkers, the steroid content and the acidity of the solution. Sustained diosgenin release in acidic aqueous solution (pH 6.0) reached from 34 to 81% after 48 h.

Self-assembled hyaluronic acid nanoparticles for controlled release of agrochemicals and diosgenin

Commercial sodium hyaluronate (HA) and synthetic hydrazide-modified HA were functionalized with diosgenin and two agrochemicals (brassinosteroids DI31 and S7) with degree of substitution ranging from 5.6 to 13.1%. The HA-steroid conjugates were studied with FTIR, 1H NMR and differential scanning calorimetry. Dynamic light scattering revealed self-assembly of the HA-steroid conjugates into stable negatively charged nanoparticles of around 159nm-441nm in water, which after drying appeared as 140nm-370nm spherically shaped nanoparticles according to transmission electron microscopy. These nanoparticles exhibited almost constant release rates of steroids for the first 8h, demonstrating sustained steroids delivery for 72h in acidic medium. The nanoparticles formed from HA-steroid conjugates were not cytotoxic to human microvascular endothelial cells (HMVEC), while the HA- brassinosteroid nanoparticles showed in vitro agrochemical activity that was superior to the activity observed for the parent brassinosteroids DI31 and S7 at 10-5 to 10-7mgmL-1.