Physicochemical Characterization and In Vitro Activity of Poly(ε-Caprolactone)/Mycophenolic Acid Amorphous Solid Dispersions.

The obtention of amorphous solid dispersions (ASDs) of mycophenolic acid (MPA) in poly(ε-caprolactone) (PCL) is reported in this paper. An improvement in the bioavailability of the drug is possible thanks to the favorable specific interactions occurring in this system. Differential scanning calorimetry (DSC) was used to investigate the miscibility of PCL/MPA blends, measuring glass transition temperature (Tg) and analyzing melting point depression to obtain a negative interaction parameter, which indicates the development of favorable inter-association interactions. Fourier transform infrared spectroscopy (FTIR) was used to analyze the specific interaction occurring in the blends. Drug release measurements showed that at least 70% of the drug was released by the third day in vitro in all compositions. Finally, preliminary in vitro cell culture experiments showed a decreased number of cancerous cells over the scaffolds containing MPA, presumably arising from the anti-cancer activity attributable to MPA.

Crystallization Behavior and Mechanical Properties of Poly(ε-caprolactone) Reinforced with Barium Sulfate Submicron Particles.

Poly(ε-caprolactone) (PCL) was mixed with submicron particles of barium sulfate to obtain biodegradable radiopaque composites. X-ray images comparing with aluminum samples show that 15 wt.% barium sulfate (BaSO4) is sufficient to present radiopacity. Thermal studies by differential scanning calorimetry (DSC) show a statistically significant increase in PCL degree of crystallinity from 46% to 52% for 25 wt.% BaSO4. Non-isothermal crystallization tests were performed at different cooling rates to evaluate crystallization kinetics. The nucleation effect of BaSO4 was found to change the morphology and quantity of the primary crystals of PCL, which was also corroborated by the use of a polarized light optical microscope (PLOM). These results fit well with Avrami-Ozawa-Jeziorny model and show a secondary crystallization that contributes to an increase in crystal fraction with internal structure reorganization. The addition of barium sulfate particles in composite formulations with PCL improves stiffness but not strength for all compositions due to possible cavitation effects induced by debonding of reinforcement interphase.

Amorphous solid dispersions in poly(ε-caprolactone)/xanthohumol bioactive blends: physicochemical and mechanical characterization.

This paper reports the obtention of amorphous solid dispersions (ASDs) of xanthohumol (XH) in PCL containing up to 50 wt% of the bioactive compound in the amorphous form thanks to the advantageous specific interactions established in this system. The miscibility of the PCL/XH blends was investigated using DSC. Melting point depression analysis yielded a negative interaction parameter indicating the occurrence of favorable inter-association interactions. XRD analyses performed at room temperature agree with the crystallinity results obtained on the heating runs performed by DSC. FTIR spectroscopy reveals strong C[double bond, length as m-dash]OO-H specific interactions between the hydroxyl groups of XH and the carbonyl groups of PCL. The AFM analysis of the blends obtained by spin-coating shows the variation of crystalline morphology with composition. Finally, tensile tests reveal high toughness retention for the blends in which XH can be dispersed in the amorphous form (containing up to 50 wt% XH). In summary, PCL is a convenient matrix to disperse XH in the amorphous form, bringing the possibility of obtaining completely amorphous bioactive materials suitable for the development of non-stiff biomedical devices.

Novel Hydrogels of Chitosan and Poly(vinyl alcohol) Reinforced with Inorganic Particles of Bioactive Glass.

Chitosan (CS) and poly(vinyl alcohol) (PVA) hydrogels, a polymeric system that shows a broad potential in biomedical applications, were developed. Despite the advantages they present, their mechanical properties are insufficient to support the loads that appear on the body. Thus, it was proposed to reinforce these gels with inorganic glass particles (BG) in order to improve mechanical properties and bioactivity and to see how this reinforcement affects levofloxacin drug release kinetics. Scanning electron microscopy (SEM), X-ray diffraction (XRD), swelling tests, rheology and drug release studies characterized the resulting hydrogels. The experimental results verified the bioactivity of these gels, showed an improvement of the mechanical properties and proved that the added bioactive glass does affect the release kinetics.

Morphology and mechanical properties of poly(ethylene brassylate)/cellulose nanocrystal composites.

Poly(ethylene brassylate), a novel inexpensive biodegradable polyester, has been reinforced with cellulose nanocrystals (CNCs) with the aim of improving its thermal stability and mechanical properties. The composites have been characterized through calorimetry, tensile tests, thermogravimetry and electron microscopy. The addition of small amounts of CNCs improves both the stiffness and the ductility of the composites, suggesting the existence of some compatibilizing effect. Adding large CNC amounts increases the Young modulus (e.g., 150% for 50 wt% CNCs), but now the material shows brittle behavior. Degradation of the CNCs starts at lower temperature suggesting mutual reactivity. The SEM analysis of the composites with ductile behavior reveals the formation of a percolating network crossing through the interconnected domains that conform a PEB-rich continuous phase. Processing consisting on reinforcement dispersion by sonication followed by melt processing results in composites in which the improvement of mechanical properties does not involve any trade-off.

Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations.

In Europe, the mean incidence of urinary tract infections in intensive care units is 1.1 per 1000 patient-days. Of these cases, catheter-associated urinary tract infections (CAUTI) account for 98%. In total, CAUTI in hospitals is estimated to give additional health-care costs of £1-2.5 billion in the United Kingdom alone. This is in sharp contrast to the low cost of urinary catheters and emphasizes the need for innovative products that reduce the incidence rate of CAUTI. Ureteral stents and other urinary-tract devices suffer similar problems. Antimicrobial strategies are being developed, however, the evaluation of their efficacy is very challenging. This review aims to provide considerations and recommendations covering all relevant aspects of antimicrobial material testing, including surface characterization, biocompatibility, cytotoxicity, in vitro and in vivo tests, microbial strain selection, and hydrodynamic conditions, all in the perspective of complying to the complex pathology of device-associated urinary tract infection. The recommendations should be on the basis of standard assays to be developed which would enable comparisons of results obtained in different research labs both in industry and in academia, as well as provide industry and academia with tools to assess the antimicrobial properties for urinary tract devices in a reliable way.

Novel biodegradable and non-fouling systems for controlled-release based on poly(ε-caprolactone)/Quercetin blends and biomimetic bacterial S-layer coatings.

Quercetin is a strong antioxidant with low bioavailability due to its high crystallinity. A further drawback is that Quercetin has potentially toxic effects at high concentrations. To improve this low water solubility, as well as control the concentration of the flavonoid in the body, Quercetin is incorporated into a polymeric matrix to form an amorphous solid dispersion (ASD) stable enough to resist the recrystallization of the drug. For this purpose, miscible poly(ε-caprolactone) (PCL) and Quercetin (Q) blends are prepared, provided that they have complementary interacting groups. For compositions in which the flavonoid remains in an amorphous state thanks to the interactions with polymer chains, various PCL/Q drug release platforms are fabricated: micrometric films by solvent casting, nanometric films by spin coating, and nanofibers by electrospinning. Then, the potential use of bacterial S-layer proteins as release-preventive membranes is tested on PCL-Quercetin blends, due to their ability to construct a biomimetic coating including nanometric pores. For all the platforms, the SbpA coating can maintain a stable release under the toxicity level of Quercetin. Accordingly, a PCL/Q system with an S-layer coating allows the design of versatile bioavailable Quercetin eluting devices that prevent toxicity and biofouling issues.

Correction: Novel biodegradable and non-fouling systems for controlled-release based on poly(ε-caprolactone)/Quercetin blends and biomimetic bacterial S-layer coatings.

[This corrects the article DOI: 10.1039/C9RA04398E.].

The conformation of chloramphenicol in the ordered and disordered phases.

The conformational behavior of chloramphenicol (CHL) in the solid, liquid and vapor phases is revisited here by means of FTIR spectroscopy and QM methods. In the crystalline phase, both the IR analysis and QM computations discard the conformer proposed by Acharya et al. (Acta Cryst., 1979, B35:1360-1363) and support the one proposed by Chatterjee et al. (J. Cryst. Mol. Struct., 1979, 9:295-304), characterized by an intramolecular OH⋯O hydrogen bond in which the primary hydroxyl group acts as hydrogen bond donor. The conformational behavior of CHL in the liquid and gas phases has been analyzed using QM calculations. The Self-Consistent Reaction Field (SCRF) method with the Onsager solvation model has been used for the initial optimizations in solution, and the lowest energy conformers have been refined using the Solvation Model based on Density (SMD). In solution environment the intramolecular OH⋯O hydrogen bond in CHL is reversed so that the secondary hydroxyl group acts as hydrogen bond donor. In addition, the dichloroacetamide group folds back further over the phenyl ring to form an intramolecular CCl⋯π halogen bond. Two different halogen bonds are actually observed (each one with a different chlorine atom) resulting in two different stable conformers, that can be detected by FTIR spectroscopy due to the conformational sensitivity of the CO group to the conformation of the dichloroacetyl group. Finally, the stability of the conformers with the polarity of the medium is also discussed.

Recent developments in drug eluting devices with tailored interfacial properties.

Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings.

Competing specific interactions investigated by molecular dynamics: analysis of poly(p-dioxanone)/poly(vinylphenol) blends.

Molecular dynamics simulations (MD) were carried out to model the miscibility behavior of blends of poly(p-dioxanone) (PPDO) with poly(vinylphenol) (PVPh). The Hildebrand solubility parameters of the pure polymers and the Flory-Huggins interaction parameters of the blends at different compositions were computed. Negative interaction parameters were found across the whole range of compositions, suggesting the miscibility of the system, in agreement with the experimental results. The interaction parameter obtained from melting point depression studies was also found to be in good agreement with the value computed from the simulations. The repeat unit of PPDO contains one ether and one ester group, and both can act as hydrogen bond acceptors. The radial distribution functions (RDFs) between those groups and the hydroxyl groups of PVPh were computed to investigate the competence between the acceptor groups for the specific interactions. The RDFs indicate that interassociation occurs mainly with the ester groups, which is detrimental to the ether groups. This result was also corroborated by the analysis of the hydroxyl stretching region of the blends using Fourier transform infrared spectroscopy (FTIR). The good overall agreement found between the simulated and the experimental data reveals the importance of the molecular modeling techniques in the analysis of the miscibility behavior of polymer blends.

Poly(ethylene oxide)-b-poly(L-lactide) diblock copolymer/carbon nanotube-based nanocomposites: LiCl as supramolecular structure-directing agent.

This work relies on the CNT dispersion in either solution or a polymer matrix through the formation of a three-component supramolecular system composed of PEO-b-PLLA diblock copolymer, carbon nanotubes (CNTs), and lithium chloride. According to a one-pot procedure in solution, the "self-assembly" concept has demonstrated its efficiency using suspension tests of CNTs. Characterizations of the supramolecular system by photon correlation spectroscopy, Raman spectroscopy, and molecular dynamics simulations highlight the charge transfer interaction from the CNTs toward the PEO-b-PLLA/LiCl complex. Finally, this concept was successfully extended in bulk (absence of solvent) via melt-processing techniques by dispersing these complexes in a commercial polylactide (PLA) matrix. Electrical conductivity measurements and transmission electron microscopy attested for the remarkable dispersion of CNTs, confirming the design of high-performance PLA-based materials.

Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with tertiary polyamides.

This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong hydrogen bonding has been found, and both polybases have shown similar acceptor strengths. Derivative techniques show asymmetric profiles for the free carbonyl band of the polybases, resulting in shifted band locations. The extent of the interassociation has been estimated by spectral curve fitting of the polybase carbonyl band. The results show that the interaction degree in blends with PEOX does not depend on the length of the poly(monoalkyl itaconate) side group, while an inter-associating ability loss is observed in blends with PDMA as the side-group size of the polyacid increases. This different behavior is attributed to the greater interspacing between vicinal carbonyl groups in PEOX. This band shows conformational sensitivity and reflects the conformational changes that occur as the steric hindrances present in the medium (due to the bulky side groups of the polyacids) increase.