Search

Abstract: The objective of the work was to prepare chitosan–Ca–alginate microparticles that can effectively deliver 5-ASA to the colon after peroral administration. For these requirements, a spray-drying technique was applied to 5-ASA/sodium alginate aqueous solution to obtain spherical particles having a mean diameter less than 10μm. The microparticles formed were cross-linked and coated into solution of CaCl2 and chitosan to obtain stable microsystem. 1H NMR and UV–vis spectra of 5-ASA have shown no degradation when working in adequate conditions, such as light protection, freshly prepared solution and use of nitrogen to prevent the oxidative self-coupling of 5-ASA moieties. By imaging with SEM, acceptable spherical morphology was observed, but also flattened, disk-shaped particles of smooth surface and low porosity. CLSM imaging showed dominant localization of chitosan in the particle wall, while for alginate, a homogeneous distribution throughout the particle was observed giving the particles negative charge. In the FTIR spectra of 5-ASA loaded Ca–alginate microparticles the characteristic peaks of 5-ASA were not altered indicating no covalent interaction between the drug and the polymer. DSC and X-ray diffraction studies revealed that 5-ASA was molecularly dispersed within the chitosan–Ca–alginate microparticles during the production process. [Copyright &y& Elsevier]

Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 μm, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

To overcome certain problems encountered in cell therapy, particularly cell survival, lack of cell differentiation and integration in the host tissue, we developed pharmacologically active microcarriers (PAM). These biodegradable particles made with poly(D,L-lactic-co-glycolic acid) (PLGA) and coated with adhesion molecules may serve as a support for cell culture and may be used as cell carriers presenting a controlled delivery of active protein. They can thus support the survival and differentiation of the transported cells as well as their microenvironment. To develop this tool, nerve growth factor (NGF)-releasing PAM, conveying PC12 cells, were produced and characterized. Indeed, these cells have the ability to differentiate into sympathetic-like neurons after adhering to a substrate, in the presence of NGF, and can then release large amounts of dopamine. Certain parameters such as the size of the microcarriers, the conditions enabling the coating of the microparticles and the subsequent adhesion of cells were thus studied to produce optimized PAM.

Purpose: The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres., Methods: Microparticles were prepared according to the double emulsion method. PEG 400 was added with NGF in the internal aqueous phase (PEG/PLGA ratio 1/1 and 1.8/1). Its effect was investigated through interfacial tension studies. Protein stability was assessed by ELISA., Results: A novel application of PEG in protein stabilization during encapsulation was evidenced by adsorption kinetics studies. PEG 400 limited the penetration of NGF in the interfacial film of the primary emulsion. Consequently, it stabilized the NGF by reducing the contact with the organic phase. In addition, it avoided the NGF release profile to level off by limiting the irreversible NGF anchorage in the polymer layers. On the other hand, the amount of active NGF released in the early stages was increased. During microparticle preparation, NaCl could be added in the external aqueous phase to modify the structure of microparticles. This allowed to reduce the initial release rate without affecting the protein stability always encountered in the absence of PEG., Conclusions: PEG 400 appeared of major interest to achieve a continuous delivery of NGF over seven weeks from biodegradable microparticles prepared by the double emulsion technique.

The solvent extraction/evaporation process has been used to form poly(D,L-lactide-co-glycolide) (PLAGA) BCNU-loaded microspheres designed for use as intracranial controlled-release implants. Their actual payload could reach 25% with a 20-50 microns size distribution. Scanning electron microscopy showed that such carriers had a smooth surface and a spherical geometry. Differential scanning calorimetry analyses carried out on drug-loaded microspheres established that the PLAGA Tg was markedly shifted towards the low temperatures along with the disappearance of the BCNU melting endotherm. Annealing experiments performed at room temperature did not induce any change of the loaded microsphere DSC profiles. These features indicated that the BCNU acted as a plasticizer for the coating material and formed with it a solid solution. Similarly, stability of encapsulated BCNU was assessed in different conditions of storage. It appeared that drug degradation increased with temperature increase: 5.4, 8.8, 32.4 and 51.2% of decomposition after 3 month storage at -18, 4, room temperature (RT) and 37 degrees C respectively. Since the free drug was stable at 4 degrees C and experienced only 10.6% decomposition at RT during the same storage time, the state of solid solution involving the intimate mixing of the drug and the polyester in the matrix favors a progressive decomposition of BCNU. However, keeping the microspheres 6 months at -18 degrees C or 3 months at 4 degrees C prevents a loss of drug superior to 10%.

The aim of this work was to prepare biodegradable poly(D,L-lactic acid-co-glycolic acid) copolymer (PLAGA) nanoparticles by the solvent evaporation process and to incorporate an antifungal antibiotic, amphotericin B. Blank nanoparticles obtained were 130 +/- 27 nm in diameter. When amphotericin B was added in the organic phase, the final suspension showed two populations due to unbound drug. Free amphotericin B was removed by contacting the nanoparticle suspension with an adsorbent polymer. Amberlite XAD16, and subsequently ultrafiltering the medium. The drug payload was between 0.7 and 1.3%. To gain more insight in the cause of this low loading, we studied progesterone-loaded nanoparticles using PLAGA and polystyrene as models because progesterone and these polymers exhibit a degree of miscibility. In the case of polystyrene, nanoparticle drug content reached 8%.