Designed sponges based on chitosan and cyclodextrin polymer for a local release of ciprofloxacin in diabetic foot infections.

Diabetic foot infections are the most common complications requiring hospitalisation of patients with diabetes. They often result in amputation to extremities and are associated with high morbi-mortality rates, especially when bone is infected. Treatment of these complications is based on surgical procedures, nursing care and systemic antibiotic therapy for several weeks, with a significant risk of relapse. Due to low blood flow and damage caused by diabetic foot infection, blood supply is decreased, causing low antibiotic diffusion in the infected site and an increase of possible bacterial resistance, making this type of infection particularly difficult to treat. In this context, the aim of this work was to develop a medical device for local antibiotic release. The device is a lyophilized physical hydrogel, i.e a sponge based on two oppositely charged polyelectrolytes (chitosan and poly(cyclodextrin citrate)). Cyclodextrins, via inclusion complexes, increase drug bioavailability and allow an extended release. Using local release administration increases concentrations in the wound without risk of toxicity to the body and prevents the emergence of resistant bacteria. The hydrogel was characterised by rheology. After freeze-drying, a curing process was implemented. The swelling rate and cell viability were evaluated, and finally, the sponge was impregnated with a ciprofloxacin solution to evaluate its drug release profile and its antibacterial activity.

Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and in contact lenses.

Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, ß- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks.

Cyclodextrin and maltodextrin finishing of a polypropylene abdominal wall implant for the prolonged delivery of ciprofloxacin.

The aim of this work was to develop a polypropylene (PP) artificial abdominal wall implant for the prolonged release of ciprofloxacin (CFX). This sustained release effect was obtained by functionalization of the textile mesh with citric acid and hydroxypropyl-γ-cyclodextrin (HPγCD) or maltodextrin (MD). In both cases the textile finishing reaction yielded a cyclo- or malto-dextrin crosslinked polymer coating the fibers. The modified supports were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry and scanning electron microscopy. The sorption capacities and the kinetics of CFX release were studied by batch tests coupled with spectrophotometric assays. Microbiological assays were carried out on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, while proliferation and viability tests used fibroblasts. The main results were as follows. (i) Due to the differences between the range of temperature of thermal degradation of the (cyclo)dextrins polymers and of the PP fibers TGA was a reliable method for quantifying the degree of functionalization of the textiles. (ii) Both modified supports showed improved sorption/desorption capacities for CFX, compared with the virgin mesh. The HPγCD-finished support showed an increased sorption capacity and a lower release rate of CFX compared with the MD modified support. (iii) Microbiological assays confirmed the latter result, with greater sustained antibacterial activity of the HPγCD treated support. These experiments have demonstrated the role of the cyclodextrin cavity in interactions with CFX: the antibiotic was not only adsorbed via hydrogen and acid-base interactions with the polyCTR-HPγCD network, but also via host-guest complexation. (iv) Biological tests revealed a slight decrease in fibroblast proliferation after 6 days on the modified supports, but cell viability tests showed that this was not due to toxicity of the (cyclo)dextrin polymer coatings.

Lignin incorporation combined with electron-beam irradiation improves the surface water resistance of starch films.

We investigated the potential of an electron-beam post-treatment to tailor the properties of 70/30 and 80/20 wt. extruded starch-lignin films. The effect of a 400 kGy radiation on films differing essentially by the kind of lignins incorporated (lignosulfonates/alkali lignins) was assessed both at the macroscopic and the molecular levels. Changes in the polymer molecular structure were studied by IR spectroscopy, by thioacidolysis as well as by model compound experiments. Electron beam-irradiation at 400 kGy, a rather high dose for processing natural polymers, alters to some extent the mechanical resistance of the starch-based materials. However this treatment substantially reduces the hydrophilic surface properties of the films, while not harming their biodegradability. Involved in radical cross-coupling reactions, lignin phenolic compounds are likely to play a primary role in the formation of a hydrophobic condensed network. This study suggests that lower irradiation doses might yield biomaterials with improved usage properties.

Compatibilization of starch-allylurea blends by electron beam irradiation: spectroscopic monitoring and assessment of grafting efficiency.

The chemical changes induced by electron-beam irradiation of mixtures of N-allylurea (AU) and amorphized starch were studied by spectroscopic methods for identifying and monitoring the reactions providing the blend with stabilized physical properties. Spectral modifications essentially concerned the AU constituent in the irradiated mixtures. FTIR and NMR analyses were used to quantify the progress of AU conversion upon irradiation and to gain information on the structure of the products. The influence of sample temperature and moisture on AU conversion rate was examined. The kinetic treatment of conversion vs dose data, from blends with different contents in AU, suggested that the phenomenological order for the reaction rate was zero, relative to the concentration in AU. The grafting yield was determined from combined (1)H NMR data recorded after selective solubilization of the constituents allowing for extraction of AU monomer and homopolymer from the grafted polysaccharide. Graft polymerization was more efficient than homopolymerization in samples containing AU in amounts less than its limiting solubility and relatively less efficient in thermodynamically unstable blends.

Physical stabilization of starch-allylurea blends by EB-grafting: a compositional and structural study.

A structural and compositional study of thermoplastic blends prepared from native potato starch (NPS) and various amounts of allylurea (AU) was performed to gain a better understanding of possible radiochemical routes to physically stable materials. The blends, mixed at ca. 130 degrees C, were studied in the form of 150 microns-thick films. Upon aging at room temperature, the samples obtained from these blends exhibit macroscopic phase separation under the form of allylurea blooming at their surface. The maximal compatibility of allylurea in amorphized potato starch was assessed by gravimetry and compared to that of urea in mixtures with NPS prepared in similar conditions. Physical aging of the unstable blends was monitored for various initial AU contents. Electron beam (EB) processing of fresh films with AU content above the solubility limit was shown to prevent phase separation, essentially as a consequence of radiation grafting onto starch of the unsaturated additive. X-ray diffractometry was performed to control (i) the effective amorphization of starch upon mixing, (ii) the recrystallization of the incompatible AU fraction from untreated blends in the tetragonal form, and (iii) the retardation or the suppression of this phenomenon after EB processing. The physical stability of the blends treated with a sufficient radiation dose (400-800 kGy) was confirmed by dynamic thermomechanical analysis of samples submitted to various hygrometric conditioning.