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Clinical and pathological effects of different acrylic intracorneal ring segments in corneal additive surgery

The objective of this work was to evaluate the potential use of less stiff materials based on acrylic copolymers of methyl methacrylate/2-ethylhexyl acrylate (MMA/EHA) as devices to correct, stabilize and improve the effect of poly(methyl methacrylate) (PMMA) intracorneal ring segments. MMA/EHA and PMMA intracorneal ring segments were surgically implanted in the corneas of Lohmann Classic hens. The effects of the intracorneal ring segments were assessed by optical measurements and corneal tolerance was evaluated through biomicroscopic examination over a 90-day observation period and by conventional histology. The experimental results demonstrated that the intracorneal ring segments made of MMA/EHA copolymers provided a significant change in the corneal curvature and an improved in vivo response compared to those obtained for PMMA rings, which was attributed to the higher flexibility of the copolymeric materials, indicating that these systems might be considered suitable as an alternative to those currently used, for application in clinical practice.

Development of advanced biantibiotic loaded bone cement spacers for arthroplasty associated infections

The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R® acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.

Conformational study on the thermal transition of chitosan-g-poly(N-vinylcaprolactam) in aqueous solution

Conformational changes of the thermal transitions of chitosan-graft-poly(N-vinylcaprolactam) copolymers in aqueous solution were studied by varying of the length of the grafted poly(N-vinylcaprolactam) (PVCL) chains, as well as the ionic strength and the pH of the solution. The conformational properties of the copolymer were monitored by means of dynamic light scattering and ζ-potential measurements. A series of copolymers with defined molecular architecture were synthesized. Obtained results point out that hydrophobic hydration plays a crucial role on the solubility of this copolymer at neutral and slightly alkaline solutions. The evolution of the size of macromolecular aggregates indicates that, in the coil state, there is a monomodal distribution, passing through a bimodal distribution in the pre-transition region, just before the phase separation. The role of the charge of the copolymers on the cooperative transition is also analyzed. The phase transition of these amphiphilic copolymers shows a strong dependence on the ionic strength of the solution.

Amphiphilic polysaccharide nanocarriers with antioxidant properties

The development of self-assembled nanocarriers for the encapsulation of hydrophobic antioxidants is of growing interest. Self-assembled amphiphilic chitosan conjugate nanocarriers that stabilize antioxidants were prepared based on the concept that both the nanocarrier and the antioxidant bear similar hydrophobic moieties able to establish hydrophobic interactions. This work describes the preparation and characterization of a system consisting of a palmitoyl chitosan conjugate and retinyl palmitate. Palmitic acid was coupled to chitosan using a carbodiimide-mediated coupling reaction, and two different palmitoyl chitosan conjugates were obtained by varying the coupling system. Palmitoyl chitosan conjugates self-assembled to form nanoparticles in aqueous medium varying in mean average diameter (Dh) between 200 and 437 nm. Retinyl palmitate–loaded nanoparticles were prepared by a solvent displacement method using dialysis, with loading efficiencies of 77.5% and 88.6%, loading contents of 12.6% and 14.6%, and Dh values of approximately 280 nm. The zeta potential (ζ) of all palmitoyl chitosan nanoparticle were above 25 mV, but ζ slightly increased in the retinyl palmitate–loaded nanoparticle. Antioxidant activity of loaded nanoparticles was confirmed using the 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. The in vitro cytotoxicity of blank and loaded nanoparticles was determined using fibroblasts of human embryonic skin. All nanoparticles were not cytotoxic when they were tested with methylthiazol tetrazolium and lactate dehydrogenase tests. The obtained results suggest that the system has potential as a nanocarrier for dermal application. Additionally, the approach considered in this article can be expanded to other nanocarrier/antioxidant systems.

Polymeric drugs based on random copolymers with antimitotic activity.

Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-α-d-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures.

Development of bioresorbable bilayered systems for application as affordable wound dressings

The objective of this work was the preparation and evaluation of a bioresorbable bilayered system for application in the treatment of dermal lesions. The system was based on a polyesterurethane as the external layer and a gelatin membrane as the internal layer. The polyesterurethane was synthesized from poly(ε-caprolactone), polyethylene glycol of 1 or 10 kDa as a hydrophilic component or Pluronic F127 as an amphiphilic component and l-lysine ethyl ester diisocyanate as an urethane precursor. Gelatin membrane was obtained by crosslinking with the naturally occurring crosslinker genipin. Three important points were addressed in this study: the physicochemical characterization of the system, the in vitro behaviour and the in vivo performance on a full-thickness wound defect of rat. The polyesterurethane containing polyethylene glycol of 10 kDa presented the optimum properties for the designed application as to be tested in animal experiments. The in vivo results showed good healing of the lesion with the formation of epidermis similar to normal rat skin. These promising results suggest the potential of this system to be used as an affordable wound dressing in the treatment of different dermal lesions.