Comparative study of vascular prostheses coated with polycyclodextrins for controlled ciprofloxacin release

A textile polyester vascular graft was modified with cyclodextrins to obtain a new implant capable of releasing antibiotics (here ciprofloxacin, CFX) over prolonged time periods and thereby reducing the risk of post-operative infections. In this study, we compared samples modified with native and modified cyclodextrins, presenting different cavity sizes (β or γ cyclodextrins) and different substituent groups (hydroxypropyl and methyl). Drug release was measured in water, phosphate buffer pH 7.4 and blood plasma. The inclusion of CFX in the cyclodextrins cavities was observed in solution by two-dimensional (1)H NMR spectroscopy and confirmed by (1)F NMR measurements. Grafts modification with all cyclodextrins induced an increase of their sorption capacity towards CFX whose extent depended on the nature of the cyclodextrin: a 4-fold and 10-fold increase was observed in the cases of hydroxypropyl cyclodextrins and methylated β-cyclodextrin, respectively. Depending on the type of release medium and nature of CD, different CFX release kinetics were obtained. The discussion highlighted not only the role of the host guest complexation, but also that of the electrostatic interactions that occur between the anionic crosslinks of the cyclodextrins polymers, and CFX that presents a zwitterionic character. The microbiological assessment confirmed sustained CFX release in human plasma and demonstrated antibacterial efficiency of CD modified prostheses against Staphylococcus aureus and Escherichia coli for at least 24h (compared to 4h in the case of virgin grafts).     

Use of cyclodextrins as a cosmetic delivery system for fragrance materials: Linalool and benzyl acetate

The aim of this study was to increase the stability and water solubility of fragrance materials, to provide controlled release of these compounds, and to convert these substances from liquid to powder form by preparing their inclusion complexes with cyclodextrins (CDs). For this purpose, linalool and benzyl acetate were chosen as the fragrance materials. The use of beta-cyclodextrin (beta CD) and 2-hydroxypropyl-beta-cyclodextrin (2-HP beta CD) for increasing the solubility of these 2 fragrance materials was studied. Linalool and benzyl acetate gave a B-type diagram with beta CD, whereas they gave an A(L)-type diagram with 2-HP beta CD. Therefore, complexes of fragrance materials with 2-HP beta CD at 1:1 and 1:2 molar ratios (guest:host) were prepared. The formation of inclusion complexes was confirmed using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and circular dichroism spectroscopy. The results of the solubility studies showed that preparing the inclusion complex with 2-HP beta CD at a 1:1 molar ratio increased the solubility of linalool 5.9-fold and that of benzyl acetate 4.2-fold, whereas the complexes at a 1:2 molar ratio increased the solubility 6.4- and 4.5-fold for linalool and benzyl acetate, respectively. The stability and in vitro release studies were performed on the gel formulations prepared using uncomplexed fragrance materials or inclusion complexes of fragrance materials at a 1:1 molar ratio. It was observed that the volatility of both fragrance materials was decreased by preparing the inclusion complexes with 2-HP beta CD. Also, in vitro release data indicated that controlled release of fragrances could be possible if inclusion complexes were prepared.     

Vascular prostheses with controlled release of antibiotics Part 2. In vitro biological evaluation of vascular prostheses treated by cyclodextrins

Viability tests by the colony forming method show no toxicity for all CDs (beta-CD, gamma-CD, HPbeta-CD and HPgamma-CD) and their associated polymer. A survival rate of 100% is observed for all CDs at high concentration 400 ppm. Proliferation tests revealed a low proliferation of L132 cells on grafted vascular prostheses and untreated prostheses and good proliferation on Melinex (film form of PET). A proliferation of 17% is observed after 3 days of incubation and decrease at 4% after 6 days on prostheses. Melinex exhibits a proliferation rate as the controls. Vitality tests confirm proliferation tests and show a good vitality of cells even for low cell amounts. From these experiments it becomes obvious that the decreasing proliferation rate is not a cytotoxic effect but is due to the chemical and/or physical surface characteristics. A similar result is obtained for cell adhesion kinetics between grafted vascular prostheses and control. After 2 h adhesion, a lower adhesion is observed on untreated prostheses. Theses results were confirmed by immunochemistry and morphology tests. This cell adhesion inhibiting effect of the PET prostheses contributes to a better "survival" of vascular prostheses without secondary obstruction or stenosis.     

Interactions of some modified mono- and bis-beta-cyclodextrins with bovine serum albumin

Two mono-substituted beta-cyclodextrins and two bridged bis-beta-cyclodextrins, that is, mono(6-(2-aminoethylamino)-6-deoxy)-beta-cyclodextrin (1), mono(6-(2-(2-aminoethylamino)ethylamino)-6-deoxy)-beta-cyclodextrin (2), ethylene-1,2-diamino bis-6-(6-deoxy-beta-cyclodextrin) (3), and iminodiethylene-2,2'-diamino bis-6-(6-deoxy-beta-cyclodextrin) (4), were prepared from beta-cyclodextrin. Their binding ability with bovine serum albumin as a model protein was investigated through proton magnetic resonance (1H NMR), ultraviolet visible spectroscopy (UV-vis), circular dichroism (CD), and fluorescence spectroscopy. In the 1H NMR spectra of the modified cyclodextrins, the resolution of proton signals decreases after the addition of BSA. From the UV and CD spectra, it is found that both the UV absorption and the alpha-helix content of BSA increase with the concentration of the modified cyclodextrins. The protein-ligand interactions cause a fluorescence quenching. The quenching constants are determined using the Stern-Volmer equation to provide an observation of the binding affinity between modified cyclodextrins and BSA. All these results indicate that the modified cyclodextrins can interact with BSA and the bridged bis(beta-cyclodextrin)s (3 and 4) have much stronger interactions than the mono-substituted beta-cyclodextrins (1 and 2). The strong binding stability of bis-cyclodextrins should be attributed to the cooperative effect of two adjacent cyclodextrin moieties. Job's plot shows that the complex stoichiometries of BSA to the modified cyclodextrins were 1:4 for 1 and 2, as well as 1:3 for 3 and 4, respectively.     

Encapsulation of citral isomers in extracted lemongrass oil with cyclodextrins: molecular modeling and physicochemical characterizations

The complexation between two isomers of citral in lemongrass oil and varying types of cyclodextrins (CDs), α-CD, β-CD, and HP-β-CD, were studied by molecular modeling and physicochemical characterization. The results obtained revealed that the most favorable complex formation governing between citrals in lemongrass oil and CDs were found at a 1:2 mole ratio for all CDs. Complex formation between E-citral and CD was more favorable than between Z-citral and CD. The thermal stability of the inclusion complex was observed compared to the citral in the lemongrass oil. The release time course of citral from the inclusion complex was the diffusion control, and it correlated well with Avrami's equation. The release rate constants of the E- and Z-citral inclusion complexes at 50 °C, 50% RH were observed at 1.32×10(-2) h(-1) and 1.43×10(-2) h(-1) respectively.     

Effects of diffused soluble steroid on capsules around experimental breast prostheses in rats.

Saline-filled miniprostheses were implanted beneath the dorsal panniculus carnosus of rats. The control prostheses contained only saline, while the experimental prostheses contained soluble methylprednisolone sodium succinate. At 10-day intervals the in situ compressibility of the tissue mound around the implants was measured mechanically. At 60 and 120 days, the control mounds were harder than those around the steroid prostheses, and the control prostheses were surrounded by a thicker capsular membrane. The control capsules contained more non-collagenous protein than the steroid modified capsules. We suggest that this non-collagenous protein may be related to the proteopolysaccharide cement which binds the fibers of immature scar together--and that the effect of our steroid treatment was to reduce this proteopolysaccharide component of the capsule membrane and thereby cause its dissolution.     

Two independent ways of preparing hypercharged hydrolyzable polyaminorotaxane

The aim of this work is to synthesize new PEO-based polyrotaxanes from modified cyclodextrins. Two strategies are discussed and compared. In the first, a pseudopolyrotaxane was formed between alpha,omega- PEO dimethacrylate and alpha-cyclodextrin. A coupling reaction between 1-pyrenebutyric acid N-hydroxysuccinimide ester was carried out to block the cyclic molecules onto the PEO. Cyclodextrins of the supramolecular assemblies were then oxidized using sodium periodate and reacted with spermine to form a potentially highly charged polyrotaxane. In the second strategy, cyclodextrins were first modified, and used to form the polyrotaxane through the pseudopolyrotaxane synthesis followed by the blocking reaction. Acidic titration allowed quantifying the number of amine functions borne by the supramolecular assemblies through two variables: the number of rings per polymer chain and the number of spermine groups per cyclic molecule. The supramolecules obtained by both strategies are discussed.     

Results of reaugmentation with MISTI prostheses after failure of smooth silicone prostheses.

In 1988 and 1989, we replaced smooth silicone double-lumen implants with Molecular Impact Surface Textured Implants (MISTIs) in 28 of our patients. Of these, 20 had experienced recurrent capsular contracture and sought an alternative prosthesis that would provide long-term relief from this problem, and 8 simply wanted larger prostheses. Among the reaugmentation patients who had experienced recurrent contractures, 4 have had problems with the texturized implants; 1 developed an infection, and 3 developed unilateral fibrosis within weeks of surgery. The infection was resolved with antibiotics, and the fibrosis was resolved with capsulectomy, biweekly methylprednisolone irrigation in the surgical pocket, and lenticular suction drainage over a 3-week period. After a 2-year follow-up, these 4 problematic patients have remained soft and asymptomatic following their treatment, and the remaining 16 patients have remained soft and asymptomatic since their surgery.     

Analysis of the surface morphology of recovered silicone mammary prostheses

The surfaces of 11 silicone mammary prostheses were examined by scanning electron microscopy (SEM) and energy dispersive x-ray spectrography (XES). Three of the prostheses were recovered from clinical cases and eight from guinea pig models. The surfaces of the prostheses were covered with an investing film and by 2- to 5-microns spheres aggregated in 40- to 200-microns-wide patches. The embeddedded spheres were blebbed and surrounded by pits. X-ray energy spectrography showed high levels of sodium, chlorine, and potassium. It is concluded from this evidence that phagocytic cells embed themselves within the envelope, perhaps by an immune-mediated phagocytic process.     

Antiseptic cyclodextrin-functionalized hydrogels and gauzes for loading and delivery of benzalkonium chloride

Prevention and management of wound infections receive a lot of attention, since the presence of micro-organisms interferes with the wound-healing process. The aim of this work was to use cyclodextrins (CDs) to endow hydrogels and gauzes with the ability to take up antiseptics and sustain their delivery for several hours. Benzalkonium chloride (BzCl) can form inclusion complexes with cross-linked CDs that regulate the release through an affinity-driven mechanism. Grafting of CDs to cotton gauzes using citric acid as the linker, at 190?°C and for 15?min, led to grafting yields of about 148%, much larger than those obtained at 180?°C or with shorter reaction times. Microbiological tests revealed that the BzCl-loaded networks can inhibit the growth of Staphylococcus epidermidis and Escherichia coli both on agar plates and in liquid medium. Furthermore, the antiseptic-loaded gauzes were able to inhibit biofilm formation by Staphylococcus aureus RN1HG pMV158GFP when applied in early stages of biofilm formation and could reduce the number of living cells in preformed biofilms grown in a chronic wound biofilm model. These findings highlight the role of CDs as main components of hydrogels and gauzes for the efficient delivery of antiseptics.     

Retinal prostheses: Clinical results and future challenges

Retinal prostheses aim at restoring visual perception in blind patients affected by retinal diseases leading to the loss of photoreceptors, such as age-related macular degeneration or retinitis pigmentosa. Recent clinical trials have demonstrated the feasibility of this approach for restoring useful vision. Despite a limited number of electrodes (60), and therefore of pixels, some patients were able to read words and to recognize high-contrast objects. Face recognition and independent locomotion in unknown urban environments imply technological breakthroughs to increase the number and density of electrodes. This review presents recent clinical results and discusses future solutions to answer the major technological challenges.     

The Role of <Emphasis Type="SmallCaps">l</Emphasis>-arginine in Inclusion Complexes of Omeprazole with Cyclodextrins

In this study, we investigate how the effect of l-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K_1:1) of the inclusion complexes formed between OME and each cyclodextrin, β-cyclodextrin (βCD), and methyl-β-cyclodextrin (MβCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:βCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.     

Mechanisms of enantiomeric resolution in cyclodextrin-modified capillary electrophoretic separations of binaphthyl compounds

The enantiomers of 1,1′-bi-2-naphthol, 1,1′-binaphthyl diyl hydrogen phosphate, and 1,1′-binaphthyldicarboxylic acid are separated using capillary electrophoresis with cyclodextrins added to the running buffer. It is demonstrated that the type and concentration of cyclodextrin employed are critical for maximum enantiomeric resolution. A modified version of a previously described model of enantiomeric separations in capillary electrophoresis is shown to support the observed separation behavior. Molecular modeling is employed to calculate interaction energies between the various enantiomers and cyclodextrins. A reasonable correlation between these computationally derived interaction energies and separation behavior resulted from a statistical mechanical treatment of the molecular modeling data. The importance of hydrogen bonding in inclusion complex formation was probed and the effects of minimization and solvation in molecular modeling calculations are also discussed. © 1995 Wiley-Liss, Inc.     

Formation of inclusion complexes between cyclodextrins and aromatic compounds under pressurized carbon dioxide

The effects of moisture content, pressure and temperature on the formation of inclusion complexes with cyclodextrins under pressurized carbon dioxide (CO₂) were studied to determine the optimal conditions for the recovery of aromatic compounds after extraction with supercritical or liquid CO₂. The presence of water in the cyclodextrin was essential for the formation of inclusion complex. However, an excess of water lowered the amount of inclusion complex due to inhibition of contact with CO₂. As the pressure increased under a constant temperature, the amount of inclusion complex increased until CO₂ became liquid, where the formation of inclusion complex started to decline. The amount of inclusion complex for modified cyclodextrins was very little, because the cyclodextrins became paste- or candy-like by the addition of a small amount of water.     

Enhanced Solubilisation of Six PAHs by Three Synthetic Cyclodextrins for Remediation Applications: Molecular Modelling of the Inclusion Complexes

Solubilisation of six polycyclic aromatic hydrocarbons (PAHs) (acenaphthene, anthracene, fluoranthene, fluorene, phenanthrene and pyrene) by three synthetic cyclodextrins (CDs) (2-hydroxypropyl-β-CD, hydroxypropyl-γ-CD and ramdomly methylated-β-CD) was investigated in order to select the CD which presents the greatest increase in solubility and better complexation parameters for its use in contaminated scenarios. The presence of the three cyclodextrins greatly enhanced the apparent water solubility of all the PAHs through the formation of inclusion complexes of 1∶1 stoichiometry. Anthracene, fluoranthene, fluorene and phenanthrene clearly presented a higher solubility when β-CD derivatives were used, and especially the complexes with the ramdomly methylated-β-CD were favoured. On the contrary, pyrene presented its best solubility results when using 2-hydroxypropyl-γ-CD, but for acenaphthene the use of any of the three CDs gave the same results. Complementary to experimental phase-solubility studies, a more in-depth estimation of the inclusion process for the different complexes was carried out using molecular modelling in order to find a correlation between the degree of solubilisation and the fit of PAH molecules within the cavity of the different CDs and to know the predominant driving forces of the complexation.     

Treatment of midfacial defects using prostheses supported by ITI dental implants

The purpose of this study was to evaluate retrospectively the use of ITI dental implants used for anchoring facial prostheses in the restorative treatment of midface defects. The authors analyzed the clinical data of 26 patients with orbital defects (n = 11), orbitonasal defects (n = 4), orbitonasomaxillary defects (n = 3), and nasal defects (n = 8). Data included age, sex, primary disease, implant position, implant length, implant failure, prosthetic attachment, radiation therapy, and peri-implant skin reactions. Follow-up was at 1, 3, 6, and 12 months and then on a yearly basis. The authors noted the status of healing and complications, if any. In total, 62 implants were placed as follows: 27 (43.5 percent) for orbital prostheses, 12 (19.4 percent) for orbitonasal prostheses, 14 (22.6 percent) for orbitonasomaxillary prostheses, and nine (14.5 percent) for nasal prostheses. Thirty-eight implants (61.3 percent) were placed in previously irradiated areas in 18 patients (69.2 percent). Mild skin reactions together with mild accumulation of sebaceous crusting around implants were recorded in 14.2 percent of the skin observations. No patient experienced severe inflammation requiring administration of systemic antibiotics or surgical revision. Implant success was 100 percent in both irradiated and nonirradiated patients. In conclusion, ITI dental implants result in a high rate of success in retaining midface prostheses and offer good stability and aesthetic satisfaction.     

Follow-up visits as a measure of adaptation process to removable prostheses

Objectives: The paper was aimed to establish the influence of some general and local factors on adaptation process to removable prostheses (RPs). The adaptation process is a complex issue, which is often associated with painful reactions. Those complaints force patients to visit a dentist who makes alterations to reduce the patient's discomfort. Material and methods: The study involved analysis of 300 dental records of patients who visited our Department for RPs. The authors analysed the influence of gender, age, condition of general health, maintenance of the prosthetic base tissues and the kind of prostheses on the process of adaptation. It was measured by means of a number of follow‐up visits of the patients to our polyclinic. The findings were analysed statistically by means of chi‐squared test. The level of significance was assumed to be p < 0.05. Results and conclusions: Adaptation to RPs without any correction was revealed by about one‐fifth of patients. Men adapted to RPs better than women. The biggest problems with adaptation to RPs were observed in patients using a complete and partial prosthesis simultaneously. The number of follow‐up visits by patients who were treated with RPs for the first time or had been treated before was almost the same. Adaptation of RPs on an atrophic muco‐osseous ridge was associated with more multiple visits than in the case of a well‐preserved ridge. Healthy patients adapt to RPs better than patients with systemic disorders. Taking into account the limitations of the study, the number of follow‐up visits may be used as a helpful indicator of the adaptation process.     

Diversity in the supramolecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H-benzimidazole with modified cyclodextrins: Implications for physicochemical properties and antiparasitic activity

The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H-benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job's plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host-guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2.     

Influence of biosurfactants from probiotic bacteria on formation of biofilms on voice prostheses

Biofilms were grown on preconditioned voice prostheses with biosurfactants obtained from probiotic bacteria Lactococcus lactis 53 and Streptococcus thermophilus A in an artificial throat model. Both biosurfactants greatly reduced microbial numbers on prostheses and also induced a decrease in the airflow resistance that occurs on voice prostheses after biofilm formation. This study presents a promising strategy for prolonging the lifespan of voice prostheses.     

Small-calibre vascular grafting into the rat abdominal aorta with biodegradable prostheses

130 Male Wistar rats, 2-3 months old and weighing 250-350 g were operated on to implant biodegradable small-calibre vascular prostheses (length 10 mm; internal diameter 1.5 mm) in their infrarenal abdominal aorta. The mean operation time was 40 min, the mean aortic cross-clamping time 25 min. The early patency rate was 100%, the late patency rate was 97.7%, and the operative mortality was 3.1%. Microscopical examination of the biodegradable prostheses from 1 h up to 1 year after implantation demonstrated reproducible morphological results; in these prostheses a new arterial wall regenerated which had a structure very similar to the normal arterial wall. It was concluded that the rat is an appropriate experimental laboratory animal for testing new types of small-calibre vascular prostheses.