Supercritical fluid (SCF)-assisted preparation of cyclodextrin-based poly(pseudo)rotaxanes for transdermal purposes.

This study aims to investigate the effect of the preparation of solid dispersions using supercritical CO2 (scCO2) on the physicochemical properties and the performance of supramolecular gels based on polymer-cyclodextrin (CD) interactions (named poly(pseudo)rotaxanes, PPR) envisaging a transdermal administration. Solid dispersions containing Soluplus®, the antihypertensive drug carvedilol (CAR), and CD (αCD or HPßCD) were prepared and characterized by HPLC, XRPD, FTIR, and DSC. PPRs prepared from solid dispersions (SCF gels) and the corresponding physical mixtures (PM gels) were analyzed regarding rheology, morphology, in vitro drug diffusion, and ex vivo drug skin permeation. The application of scCO2 led to the loss of the crystalline lattice of CAR while preserving its chemical identity. On the contrary, αCD crystals were still present in the SCF solid dispersions. SCF gels were more uniform than their corresponding PM, and the supercritical treatment resulted in changes in the rheological behavior, reducing the viscosity. CAR in vitro diffusion was significantly higher (p < 0.05) for the αCD-based SCF gel than its corresponding PM gel. Drug skin permeation showed a significant increase in drug flux from CD-based SCF gels (containing αCD or HPßCD) compared to corresponding PM gels. Additionally, the pretreatment of the skin with αCD exhibited increased CAR permeation, suggesting an interaction between αCD and the skin membrane. Results evidenced that SCF processing decisively modified the properties of the supramolecular gels, particularly those prepared with αCD.

Evaluación del impacto social de la carrera de estomatología / Evaluation of the social impact of the dental medicine major

Introducción: El impacto y la pertinencia social han constituido elementos relevantes al momento de conocer el desempeño de la educación superior en un país. En el caso de las universidades de ciencias médicas, que se encargan de la formación integral de los profesionales de la salud, el mejoramiento continuo de la calidad de los procesos académicos representa una prioridad para cumplir con el encargo social. Objetivo: Reflexionar sobre la evaluación del impacto social de la carrera de estomatología de la Universidad de Ciencias Médicas de La Habana. Posicionamiento de los autores: La carrera de estomatología tiene una tradición de más de cien años. Ha sido reconocida su calidad y excelencia a través de evaluaciones externas que han mostrado fortalezas en la variable pertinencia e impacto social. Sin embargo, es necesario evaluar el impacto social no solo desde el punto de vista de la satisfacción de egresados y empleadores por la formación recibida, sino en aspectos como desempeño profesional, trabajo en equipo, impacto en la salud bucal de la población, entre otros. Conclusiones: La carrera de estomatología tiene un alto reconocimiento, que se demuestra en el vínculo de los profesores y estudiantes en la solución de los problemas de salud bucal. No obstante, no se ha estimado evaluar otros impactos vinculados al desarrollo de los egresados en la investigación científica, sus expectativas, sus motivaciones y su superación profesional, los cuales, definitivamente, contribuyen al perfeccionamiento, la pertinencia y la calidad de la carrera(AU)

Introduction: Social impact and pertinence have been relevant elements at the time of knowing the performance of higher education in a country. In the case of universities of medical sciences, responsible for the comprehensive training of health professionals, the continuous improvement of the quality of academic processes represents a priority for accomplishing the social task. Objective: To reflect about the evaluation of the social impact of the dental medicine major of the University of Medical Sciences of Havana. Authors' stance: The dental medicine major has a tradition of more than a hundred years. Its quality and excellence have been recognized through external evaluations that have shown strengths in the variable social impact and pertinence. However, it is necessary to evaluate social impact not only from the point of view of the graduates' and employers' satisfaction with the offered training, but also in terms of professional performance, teamwork, impact on the oral health of the population, among others. Conclusions: The dental medicine major has a high recognition, demonstrated thought the connection among professors and students for the solution of oral health problems. However, it has not been considered to evaluate other impacts associated to the development of graduates in scientific research, their expectations, their motivations and professional upgrading, which definitely contribute to the improvement, relevance and quality of the major(AU)

Poly(pseudo)rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers.

This work aimed to develop water-based formulations for onychomycosis topical treatment using micelles of small pegylated surfactants associated with α-cyclodextrin (αCD) to deliver terbinafine to the nail. Kolliphor® RH40 (RH40) and Gelucire® 48/16 (GEL) single and mixed micelles (RH40:GEL 1:1) were prepared. αCD was added to the surfactants dispersions to form poly(pseudo)rotaxanes (PPR). Formulations were characterized in terms of drug solubilization (3 to 34-fold increase), particle size (9-11 nm) and Z-potential (+0.3 - +1.96 mV), blood compatibility (non-hemolytic), rheological behavior (solid-like viscoelastic properties after 5-10% αCD addition), drug release and interaction with the nail plate. GEL micelles and surfactant-10% αCD PPRs notably hydrated the nail plate. The high viscosity of PPR led to a slower drug release, except for RH40:GEL +10% αCD that surprisingly released terbinafine faster. The RH40:GEL +10% αCD formulation delivered twice more amount of terbinafine to deeper regions of nail plate compared to other formulations. The results evidenced the potential of PPR formed by small pegylated surfactants as a water-based formulation for nail drug delivery.

Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications.

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

Influence of the carbon source on the properties of poly-(3)-hydroxybutyrate produced by Paraburkholderia xenovorans LB400 and its electrospun fibers.

Poly-3-hydroxybutyrate (PHB) is a biocompatible polymer produced by a wide variety of bacteria from different carbon sources. However, the carbon source effects on PHB properties are largely unknown. This study aimed to characterize PHB produced by Paraburkholderia xenovorans LB400 supplied with glucose (PHBg), mannitol (PHBm), or xylose (PHBx) as sole carbon sources and to evaluate their potential application as the main component of scaffolds obtained by electrospinning. The PHBs produced by strain LB400 had different molecular weights; the largest value corresponded to PHBm. The XRD-spectra revealed that PHB produced by strain LB400 from the three carbon sources are less crystalline than the commercially available polymer (PHBc). Moreover, the electrospinning process decreases even further their degree of crystallinity, which could lead to an improvement in the mechanical properties of the polymers. Relevantly, PHBx-microfibers exhibited mechanical characteristics similar to those of human skin. None of the scaffolds made of PHBs from strain LB400 grown in different carbon sources showed adverse effects on fibroblast cell growth. Thus, modifying the sugar used as the carbon source may be useful to tune the structural properties of PHB and its performance as a component of electrospun scaffolds, which may better fit specific biomedical applications.

Anandamide-nanoformulation obtained by electrospraying for cardiovascular therapy.

Anandamide (AEA), an endogenous cannabinoid, has a relevant antihypertensive effect. However, its cardioprotective role has been barely explored due to unfavorable physico-chemical properties and, sometimes, undesirable psychoactive effects. In this context, drug encapsulation in nanocarriers could overcome the limitations associated with the administration of AEA in free form. The aim of the present study was to encapsulate AEA in poly-ε-caprolactone/Pluronic® F127 nanoparticles (AEA/PCL/PF127 NPs) by means of electrospraying, to characterize their physico-chemical properties and cytocompatibility and to evaluate their effect in an in vivo model of cardiovascular remodeling caused by hypertension. AEA/PCL/PF127 NPs were characterized in terms of morphology, size, polydispersity, Z-potential, hydrophilicity, thermal and spectroscopic properties. Also, the encapsulation and loading efficiencies and in vitro release of AEA were analyzed. AEA/PCL/PF127 NPs (700-1000 nm) showed adequate cytocompatibility. For the cardiovascular remodeling studies, normotensive (WKY) and hypertensive (SHR) male rats were treated or not with AEA/PCL/PF127 NPs (5 mg/Kg, intraperitoneal injection) weekly for 1 month. Inflammatory markers and hemodynamic, structural and cardiac functional parameters were monitored. In SHR, the treatment with AEA/PCL/PF127 NPs reversed all altered cardiovascular markers and parameters (p < 0.05). Overall, nanoformulated AEA obtained by electrospraying proved to be effective for the treatment of hypertension and its comorbidities, especially cardiovascular remodeling.

Eficacia de la técnica paso-atrás en tratamientos de endodoncia en una sesión / Effectiveness of the step-back technique in single-visit endodontic treatment

Introducción: La preparación biomecánica es determinante para el éxito del tratamiento endodóntico, pues el tope apical y el límite de obturación son etapas operatorias fundamentales para garantizar el ensanchamiento del conducto manteniendo al mismo tiempo la configuración preoperatoria inicial. Objetivo: Determinar la eficacia de la técnica de instrumentación paso-atrás en tratamientos de endodoncia en una sesión. Métodos: Se realizó un estudio de intervención terapéutica en 30 pacientes mayores de 12 años de la Clínica Estomatológica Dr. Salvador Allende, municipio Cerro, La Habana, en el periodo comprendido entre diciembre de 2015 y junio de 2017. Se analizaron como variables: dolor posoperatorio, inflamación, exámenes radiográficos, éxito y fracaso de los tratamientos teniendo en cuenta condición pulpar y tipo de diente tratado. La presentación de la información se realizó mediante tablas de contingencia de dos entradas, utilizando como medida de resumen el tanto por ciento. Resultados: El 90 por ciento de los pacientes no padeció dolor posoperatorio; el 96,67 por ciento de los tratamientos fueron eficaces al no existir signos de inflamación; y el 3,3 por ciento de los exámenes radiográficos evolutivos mostró imágenes de procesos inflamatorios crónicos. Conclusiones: La técnica de instrumentación paso-atrás en el tratamiento de endodoncia en una sesión fue eficaz en la mayoría de los casos. El mayor porcentaje de pacientes tratados no refirió dolor posoperatorio ni presentó inflamación(AU)

Introduction: Biomechanical preparation is crucial for the success of endodontic treatment, since the apical top and the obturation limit are fundamental operational stages to ensure appropriate broadening of the duct maintaining the initial preoperative configuration. Objective: Determine the effectiveness of the step-back instrumentation technique in single-visit endodontic treatment. Methods: A therapeutic intervention study was conducted of 30 patients aged over 12 years at Dr. Salvador Allende Dental Clinic in the municipality of Cerro, Havana, from December 2015 to June 2017. The variables analyzed included postoperative pain, swelling, radiographic examination, success and failure of treatment based on pulp condition and type of tooth treated. Data were presented in two-entry contingency tables, with percentage as the measure of summary. Results: 90 percent of the patients did not have any postoperative pain, 96.67 percent of the treatments were effective in that there were no signs of swelling, and 3.3 percent of the evolutionary radiographic tests showed images of chronic inflammatory processes. Conclusions: The step-back instrumentation technique in single-visit endodontic treatment was found to be effective in most cases. The highest percentage of patients treated did not report any postoperative pain or swelling(AU)

Eficacia de la técnica paso-atrás en tratamientos de endodoncia en una sesión / Effectiveness of the step-back technique in single-visit endodontic treatment

Introducción: La preparación biomecánica es determinante para el éxito del tratamiento endodóntico, pues el tope apical y el límite de obturación son etapas operatorias fundamentales para garantizar el ensanchamiento del conducto manteniendo al mismo tiempo la configuración preoperatoria inicial. Objetivo: Determinar la eficacia de la técnica de instrumentación paso-atrás en tratamientos de endodoncia en una sesión. Métodos: Se realizó un estudio de intervención terapéutica en 30 pacientes mayores de 12 años de la Clínica Estomatológica Dr. Salvador Allende, municipio Cerro, La Habana, en el periodo comprendido entre diciembre de 2015 y junio de 2017. Se analizaron como variables: dolor posoperatorio, inflamación, exámenes radiográficos, éxito y fracaso de los tratamientos teniendo en cuenta condición pulpar y tipo de diente tratado. La presentación de la información se realizó mediante tablas de contingencia de dos entradas, utilizando como medida de resumen el tanto por ciento. Resultados: El 90 por ciento de los pacientes no padeció dolor posoperatorio; el 96,67 por ciento de los tratamientos fueron eficaces al no existir signos de inflamación; y el 3,3 por ciento de los exámenes radiográficos evolutivos mostró imágenes de procesos inflamatorios crónicos. Conclusiones: La técnica de instrumentación paso-atrás en el tratamiento de endodoncia en una sesión fue eficaz en la mayoría de los casos. El mayor porcentaje de pacientes tratados no refirió dolor posoperatorio ni presentó inflamación(AU)

Introduction: Biomechanical preparation is crucial for the success of endodontic treatment, since the apical top and the obturation limit are fundamental operational stages to ensure appropriate broadening of the duct maintaining the initial preoperative configuration. Objective: Determine the effectiveness of the step-back instrumentation technique in single-visit endodontic treatment. Methods: A therapeutic intervention study was conducted of 30 patients aged over 12 years at Dr. Salvador Allende Dental Clinic in the municipality of Cerro, Havana, from December 2015 to June 2017. The variables analyzed included postoperative pain, swelling, radiographic examination, success and failure of treatment based on pulp condition and type of tooth treated. Data were presented in two-entry contingency tables, with percentage as the measure of summary. Results: 90 percent of the patients did not have any postoperative pain, 96.67 percent of the treatments were effective in that there were no signs of swelling, and 3.3 percent of the evolutionary radiographic tests showed images of chronic inflammatory processes. Conclusions: The step-back instrumentation technique in single-visit endodontic treatment was found to be effective in most cases. The highest percentage of patients treated did not report any postoperative pain or swelling(AU)

Predictores de una interacción eficaz entre madre e hijo/a en contextos de riesgo psicosocial / Predictors of an Efficient Interaction between Mother and Child in Psychosocial Risk

RESUMEN Este estudio analiza la influencia de las prácticas, las metas, la representación materna de las propias acciones y la predictibilidad de prácticas y metas según los hijos/as sobre la interaccion madre-hijo/a observada en una tarea colaborativa. Las participantes fueron 82 diadas en riesgo psicosocial. Las madres reportaron las prácticas y las metas en situaciones hipotéticas y la representación de la propia acción en la interacción; los hijos/as, la predictibilidad de las prácticas y las metas de las propias madres. Los modelos de regresión muestran la influencia negativa de las prácticas coercitivas y restrictivas, la influencia positiva de la representación de la acción y de la predictibilidad de prácticas y metas en la dinámica de la interacción madre-hijo/a.

ABSTRACT This study investigates the influence of the practices, goals, maternal representation of their action and the child's readability of practices and goals on the mother-child interaction observed during a collaborative task. The participants were 82 dyads at psychosocial risk. The mothers reported their practices and goals in hypothetical situations and the representation of their actions in the interaction. Children reported the readability of mothers' practices and goals. The regression models showed the negative influence of the coercitive and restrictive practices, the positive influence of the maternal representation of their child-rearing actions and the child's readability of the practices and goals on the dynamic of the mother-child interaction.

One-step grafting of temperature-and pH-sensitive (N-vinylcaprolactam-co-4-vinylpyridine) onto silicone rubber for drug delivery.

A one-step method was implemented to graft N-vinylcaprolactam (NVCL) and 4-vinylpyridine (4VP) onto silicone rubber (SR) films using gamma radiation in order to endow the silicone surface with temperature- and pH-responsiveness, and give it the ability to host and release diclofenac in a controlled manner and thus prevent bacterial adhesion. The effects of radiation conditions (e.g., dose and monomers concentration) on the grafting percentage were evaluated, and the modified films were characterized by means of FTIR-ATR, Raman spectroscopy, calorimetry techniques (DSC and TGA) and contact angle measurements. The films responsiveness to stimuli was evaluated by recording the swelling degree of pristine and modified SR in buffer solutions (critical pH point) and as a function of changes in temperature (Upper Critical Solution Temperature, UCST). The graft copolymers of SR-g-(NVCL-co-4VP) showed good cytocompatibility against fibroblast cells for prolonged times, could host diclofenac and release it in a sustained manner for up to 24 h, and exhibited bacteriostatic activity when challenged against Escherichia coli.

Polymeric prodrug-functionalized polypropylene films for sustained release of salicylic acid.

Medical devices decorated with salicylic acid-based polymer chains (polymeric prodrug) that slowly release this anti-inflammatory and anti-biofilm drug at the implantation site were designed. A "grafting from" method was implemented to directly grow chains of a polymerizable derivative of salicylic acid (2-methacryloyloxy-benzoic acid, 2MBA) onto polypropylene (PP). PP was modified both at bulk and on the surface with poly(2MBA) by means of an oxidative pre-irradiation method ((60)Co source), in order to obtain a grafted polymer in which salicylic acid units were linked by means of labile ester bonds. The grafting percent depended on absorbed dose, reaction time, temperature and monomer concentration. The functionalized films were analyzed regarding structure (FTIR-ATR, SEM-EDX, fluorescence microscopy), temperature stability (TGA), interaction with aqueous medium (water contact angle and swelling), pH-responsive release and cytocompatibility (fibroblasts). In the obtained poly(2MBA)-grafted biomaterial, poly(2MBA) behaved as a polymeric prodrug that regulates salicylic acid release once in contact with aqueous medium, showing pH-dependent release rate.

Encapsulation of Antioxidant Gallate Derivatives in Biocompatible Poly(ε-caprolactone)-b-Pluronic-b-Poly(ε-caprolactone) Micelles.

Formulation of antioxidant agents is still a challenge that limits their application in the biomedical field. Pentablock copolymers obtained through modification of two common PEO-PPO-PEO copolymers (Pluronic F127 and F68) with poly(ε-carprolactone) (PCL) were evaluated regarding their capability to form nanocarriers suitable for gallic acid, methyl gallate, and ethyl gallate. Applying a dialysis method, PCL/F127/PCL and PCL/F68/PCL self-assembled into spherical micelles in 0.9% NaCl aqueous solution but notably differed in critical micellar concentration (CMC), micelle core hydrophobicity, and micelle size, as evidenced by pyrene fluorescence, transmission electron microscopy, and dynamic light scattering. Cytotoxicity studies showed that the copolymers were safe at concentrations well above the CMC. Transfer of gallic acid and derivatives from aqueous medium to the micelle phase was characterized in terms of distribution constant and free energy of transference, which were shown to be strongly dependent on the hydrophobicity of the gallate derivatives and the length of PCL in the pentablock copolymer. Antioxidant activity of gallates was challenged against DPPH previously loaded in PCL/F127/PCL and PCL/F68/PCL micelles. The more the hydrophobicity of the gallate derivative, the greater the capability to enter in the micelle and to consume free radicals. In vitro release studies of gallic acid, methyl gallate, and ethyl gallate from the pentablock copolymer micelles also evidenced the influence of the hydrophobicity of both the gallate derivative and the micelle core on release rate, recording a variety of release patterns. Overall, PCL/F127/PCL and PCL/F68/PCL appear as suitable nanocarriers of potent antioxidant agents in a wide range of polarities, which may be useful for diverse therapeutic applications.

Poloxamer-hydroxyethyl cellulose-α-cyclodextrin supramolecular gels for sustained release of griseofulvin.

Supramolecular gels of poloxamer-hydroxyethyl cellulose (HEC)-α-cyclodextrin (αCD) were developed aiming to obtain synergisms regarding solubilization and sustained release of griseofulvin for topical application. The effects of αCD concentration (0-10%w/w) on the phase behavior of aqueous dispersions of Pluronic(®) P123 (14%w/w) mixed with HEC (2%w/w) were evaluated at 4, 20 and 37°C. The cooperative effects of the inclusion complex formation between poly(ethylene oxide) (PEO) blocks and HEC with αCD prevented phase separation and led to supramolecular networks that solubilize the antifungal drug. Rheological and bioadhesive properties of gels with and without griseofulvin could be easily tuned modulating the polymers proportions. Supramolecular gels underwent sol-gel transition at lower temperature than P123 solely dispersions and enabled drug sustained release for at least three weeks. All gels demonstrated good biocompatibility in the HET-CAM test. Furthermore, the drug-loaded gels showed activity against Trichophyton rubrum and Trichophyton mentagrophytes and thus may be useful for the treatment of tinea capitis and other cutaneous fungal infections.

Singly and binary grafted poly(vinyl chloride) urinary catheters that elute ciprofloxacin and prevent bacteria adhesion.

Acrylic acid (AAc) and poly(ethylene glycol) methacrylate (PEGMA) were singly and dually grafted onto poly(vinyl chloride) (PVC) urinary catheters with the aim of preventing biofouling by endowing the catheters with the ability to load and release antimicrobial agents and to avoid bacteria adhesion. The polymers were grafted applying an oxidative pre-irradiation ((60)Co source) method in two steps. Grafting percentage and kinetics were evaluated by varying the absorbed pre-irradiation dose, reaction time, monomer concentration, and reaction temperature. Catheters with grafting percentages ranging from 8 to 207% were characterized regarding thermal stability, surface hydrophilicity, mechanical properties, swelling, and lubricity. The modified catheters proved to have better compatibility with fibroblast cells than PVC after long exposure times. Furthermore, grafted catheters were able to load ciprofloxacin and sustained its release in urine medium for several hours. Ciprofloxacin-loaded catheters inhibited the growth of Escherichia coli and Staphylococcus aureus in the catheter surroundings and prevented bacteria adhesion.

Acrylic polymer-grafted polypropylene sutures for covalent immobilization or reversible adsorption of vancomycin.

Glycidyl methacrylate (GMA) and acrylic acid (AAc) were separately grafted onto polypropylene (PP) monofilament sutures by means of pre-irradiation using a (60)Co γ-source, with the purpose of loading vancomycin via (i) covalent immobilization through the glycidyl groups of GMA and (ii) ionic interaction with AAc moieties. The effect of absorbed radiation dose, monomer concentration, temperature and reaction time on the grafting degree was evaluated in detail. GMA grafting ranged from 25% to 800% while the grafting yield of AAc onto PP could be tuned between 9% and 454%, at doses from 5 to 50 kGy and a dose rate 13.7 kGy/h. Grafting of GMA or AAc decreased the decomposition temperature and made the sutures swellable to a certain extent. GMA grafting led to a continuous, smooth and thick coating, which was suitable for immobilization of up to 1.9 µg vancomycin per gram. The immobilized vancomycin enabled a reduction in the Staphylococcus aureus CFU adhered to the suture surface. On the other hand, dried AAc-functionalized sutures exhibited a rough and cracked surface which was responsible for a minor increase in the coefficient of friction. PP-g-AAc sutures exhibited pH-dependent swelling and remarkably high capability to host vancomycin (up to 109.9 mg/g), particularly those with an intermediate degree of grafting. Some AAc-functionalized sutures were shown able to inhibit bacterial growth after successive challenges with fresh lawns. Therefore, tuning the yield of grafting of GMA or AAc may enable the preparation of drug-suture combination products that retain or release, respectively, antimicrobial agents.

ß-Cyclodextrin hydrogels for the ocular release of antibacterial thiosemicarbazones.

Two types of hydrophilic networks with conjugated beta-cyclodextrin (ß-CD) were developed with the aim of engineering useful platforms for the localized release of an antimicrobial 5,6-dimethoxy-1-indanone N4-allyl thiosemicarbazone (TSC) in the eye and its potential application in ophthalmic diseases. Poly(2-hydroxyethyl methacrylate) soft contact lenses (SCLs) displaying ß-CD, namely pHEMA-co-ß-CD, and super-hydrophilic hydrogels (SHHs) of directly cross-linked hydroxypropyl-ß-CD were synthesized and characterized regarding their structure (ATR/FT-IR), drug loading capacity, swelling and in vitro release in artificial lacrimal fluid. Incorporation of TSC to the networks was carried out both during polymerization (DP method) and after synthesis (PP method). The first method led to similar drug loads in all the hydrogels, with minor drug loss during the washing steps to remove unreacted monomers, while the second method evidenced the influence of structural parameters on the loading efficiency (proportion of CD units, mesh size, swelling degree). Both systems provided a controlled TSC release for at least two weeks, TSC concentrations (up to 4000µg/g dry hydrogel) being within an optimal therapeutic window for the antimicrobial ocular treatment. Microbiological tests against P. aeruginosa and S. aureus confirmed the ability of TSC-loaded pHEMA-co-ß-CD network to inhibit bacterial growth.

Temperature-sensitive gels for intratumoral delivery of ß-lapachone: effect of cyclodextrins and ethanol.

This work evaluated the potential of Pluronics (varieties F127 and P123) in combination with solubilizing agents to be used as syringeable in situ gelling depots of intratumoral ß-lapachone (ßLAP). Pluronic dispersions prepared at various concentrations in the absence and the presence of ethanol and randomly methylated ß-cyclodextrin (RMßCD) were characterized regarding their rheological properties, drug solubilization capacity, and in vitro release. Pluronic F127 (18-23%) formulations combined high ability to solubilize ßLAP (enhancement solubility factor up to 50), adequate gel temperature range (over 25 °C), and gel strength at 37 °C enough to guarantee the permanence of the formulation in the administration site for a period of time. ßLAP release rate was finely tuned by the concentration of the polymer and the addition of RMßCD (diffusion coefficient ranging between 9 and 69 µg · cm(-2)). The ethanol increases ßLAP release rate but simultaneously led to weak gels. This paper shows that ßLAP formulations involving temperature-reversible Pluronic gels may be suitable for intratumoral drug delivery purposes.

Biofilm inhibition and drug-eluting properties of novel DMAEMA-modified polyethylene and silicone rubber surfaces.

Poly(2-(dimethylaminoethyl) methacrylate) (pDMAEMA) was grafted to low density polyethylene (LDPE) and silicone rubber (SR) in order to make them less susceptible to microbial biofilm formation. The direct grafting of DMAEMA using γ-rays was an efficient and fast procedure for obtaining modified materials, which could be quaternized in a second step using methyl iodide. Raman spectroscopy showed that the grafting occurred only at the surface of the LDPE, but both at the surface and in the bulk of the SR. Consequently, the grafted chains caused changes in the surface-related features of the LDPE (water contact angle and viscoelastic behavior in the dry state) and in the bulk-related properties of the SR (swelling and viscoelasticity in the swollen state). The microbiological assays revealed that the grafted DMAEMA reduced Candida albicans biofilm formation (almost no biofilm on SR), while the quaternized surfaces inhibited C. albicans and Staphylococcus aureus biofilm by more than 99% compared to pristine materials. Modified LDPE and SR were capable of holding considerable amounts of nalidixic acid, an anionic antimicrobial drug, and sustained the release for several hours. In addition, the grafted materials were cytocompatible (fibroblast cell survival > 70%). In conclusion, these materials have the ability to inhibit microbial biofilm formation and at the same time act as drug-eluting systems, and for that reason may hold great promise for anti-biofouling applications.

Stimuli-responsive networks grafted onto polypropylene for the sustained delivery of NSAIDs.

Co-polymers of N-isopropyl acrylamide (NIPAAm) and N-(3-aminopropyl) methacrylamide hydrochloride (APMA) were grafted on polypropylene (PP) films by means of a γ-ray pre-irradiation method, with the aim of developing medical devices able to load non-steroidal anti-inflammatory drugs (NSAIDs) and to control their release under physiological conditions. The NIPAAm/APMA molar ratios in the grafts, estimated by Fourier transform infrared attenuated total reflection spectroscopy and X-ray photoelectron spectroscopy analysis, were 4.76 and 1.23 for PP-g-(1M NIPAAm-r-0.5M APMA) and PP-g-(1M NIPAAm-r-1M APMA), respectively. By varying the reaction time, different degrees of grafting were achieved, while the monomer ratio was kept constant. PP-g-(NIPAAm-r-APMA) films showed temperature-responsive swelling, smaller friction coefficients, hemolysis and thrombogenicity and higher cell compatibility, did not elicit secretion of cytokines, and took up remarkable amounts of diclofenac and ibuprofen and sustained delivery for several hours in phosphate buffer, pH 7.4. Coating with carboxymethyl dextran of diclofenac-loaded PP-g-(NIPAAm-r-APMA) films caused a minor discharge of the drug but did not alter the drug release rate.