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1.
ACS Biomater Sci Eng ; 10(2): 1162-1172, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38183269

RESUMEN

Over the past decade, superhydrophilic zwitterionic surfaces, slippery liquid-infused porous surfaces, covalently attached liquid-like surfaces, and superhydrophobic surfaces have emerged as the most promising strategies to prevent biofouling on biomedical devices. Despite working through different mechanisms, they have demonstrated superior efficacy in preventing the adhesion of biomolecules (e.g., proteins and bacteria) compared with conventional material surfaces. However, their potential in combating catheter-associated urinary tract infection (CAUTI) remains uncertain. In this research, we present the fabrication of these four coatings for urinary catheters and conduct a comparative assessment of their antifouling properties through a stepwise approach. Notably, the superhydrophilic zwitterionic coating demonstrated the highest antifouling activity, reducing 72.3% of fibrinogen deposition and over 75% of bacterial adhesion (Escherichia coli and Staphylococcus aureus) when compared with an uncoated polyvinyl chloride (PVC) surface. The zwitterionic coating also exhibited robust repellence against blood and improved surface lubricity, decreasing the dynamic coefficient of friction from 0.63 to 0.35 as compared with the PVC surface. Despite the fact that the superhydrophilic zwitterionic and hydrophobic liquid-like surfaces showed great promise in retarding crystalline biofilm formation in the presence of Proteus mirabilis, it is worth noting that their long-term antifouling efficacy may be compromised by the proliferation and migration of colonized bacteria as they are unable to kill them or inhibit their swarming. These findings underscore both the potential and limitations of these ultralow fouling materials as urinary catheter coatings for preventing CAUTI.


Asunto(s)
Incrustaciones Biológicas , Infecciones Urinarias , Humanos , Infecciones Urinarias/prevención & control , Catéteres Urinarios/efectos adversos , Catéteres Urinarios/microbiología , Incrustaciones Biológicas/prevención & control , Escherichia coli , Bacterias , Interacciones Hidrofóbicas e Hidrofílicas
2.
Int J Pharm ; 651: 123791, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38195031

RESUMEN

Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NH4HCO3 was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND). Moreover, it could improve the chemical stability of the drug and the dissolution performance of compacts relative to classical moisture-based compacts upon microwaving. Further mechanistic study suggested that the in situ amorphization occurred prior to the in situ salt formation, especially in formulations with low drug loadings and high solid salt mass ratios. For compacts with low polymer ratios, in situ salt formation took place subsequently, where the previously amorphized IND within compacts could interact with the NH3 gas produced in situ by the decomposition of NH4HCO3 and form the ammonium IND salt. Microwaving time showed great impacts on the decomposition of NH4HCO3 and the in situ generation of water and NH3, which indirectly affected the amorphization and salt formation of IND. In comparison to the moisture-based systems, the NH4HCO3-based system showed a number of advantages, including the reduced potential of IND hydrolysis due to the absence of absorbed moisture, a wider category of applicable polymeric carriers other than hygroscopic polymers, and an increase in drug loading up to 50% (w/w).


Asunto(s)
Microondas , Sales (Química) , Estabilidad de Medicamentos , Cristalización , Polímeros/química , Solubilidad
3.
Biomater Adv ; 157: 213735, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38154402

RESUMEN

Inflammatory bowel disease (IBD) are chronic inflammatory conditions which cause significant patient morbidity. Local drug delivery to the colon can improve treatment efficacy and reduce side effects associated with IBD treatment. Smart drug delivery systems are designed to regulate the release of therapeutic agents at the desired site of action. pH-responsive drug carriers have been previously utilised for improved oral drug delivery beyond stomach harsh conditions. Additionally, the colon possesses a diverse microbiome secreting bioactive molecules e.g., enzymes, that can be exploited for targeted drug delivery. We herein synthesised and characterised a 2-hydroxyethyl methacrylate and methacrylic acid copolymer, crosslinked with an azobenzyl crosslinker, that displayed pH- and enzyme-responsive properties. The swelling and drug release from hydrogel were analysed in pH 1.2, 6.5 and 7.4 buffers, and in the presence of rat caecal matter using metronidazole and mesalamine as model BCS Class I and IV drugs, respectively. Swelling studies displayed pH-responsive swelling behaviour, where swelling was maximum at pH 7.4 and minimum at pH 1.2 (69 % versus 32 %). Consequently, drug release was limited in gastric and small intestinal conditions but increased significantly when exposed to colonic conditions containing caecal matter. This system displays promising capacity for achieving colon-targeted drug delivery with enhanced dissolution of poorly water-soluble drugs for local treatment of IBD and other colon-targeted therapies.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Agua , Ratas , Animales , Humanos , Agua/farmacología , Sistemas de Liberación de Medicamentos , Portadores de Fármacos , Colon , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico
4.
Proc Inst Mech Eng H ; : 9544119231178468, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37300485

RESUMEN

Despite the extensive use of intermittent catheters (ICs) in healthcare, various issues persist for long-term IC users, such as pain, discomfort, infection, and tissue damage, including strictures, scarring and micro-abrasions. A lubricous IC surface is considered necessary to reduce patient pain and trauma, and therefore is a primary focus of IC development to improve patient comfort. While an important consideration, other factors should be routinely investigated to inform future IC development. An array of in vitro tests should be employed to assess IC's lubricity, biocompatibility and the risk of urinary tract infection development associated with their use. Herein, we highlight the importance of current in vitro characterisation techniques, the demand for optimisation and an unmet need to develop a universal 'toolkit' to assess IC properties.

5.
Analyst ; 148(9): 2002-2011, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37039025

RESUMEN

Biofilms are complex environments where matrix effects from components such as extracellular polymeric substances and proteins can strongly affect SERS performance. Here the interactions between SERS-enhancing Ag and Au particles were studied using ex situ biofilms (es-biofilms), which were more homogenous than in situ biofilm samples. This allowed systematic quantitative studies, where samples could be accurately diluted and analysed, to be carried out. Strong signals from intrinsic marker compounds were found for the Pseudomonas aeruginosa and Staphylococcus aureus extracted es-biofilms, which the standard addition method showed were due to 2 × 10-3 mol dm-3 pyocyanin or the equivalent of 1 × 10-4 mol dm-3 adenine, respectively. The es-biofilms hindered aggregation of Ag colloids more than Au but for both Au and Ag nanospheres the presence of es-biofilm reduced SERS signals through a combination of poorer aggregation and blocking of surface sites. For Ag, the effect of lower aggregation was to reduce the signals by a factor of ca. 2×, while site blocking gave a further 10× reduction for adenine. Similar results were found for Au nanospheres with adenine, although these particles gave low enhancement with pyocyanin. Nanostars were found to be unaffected by reduced aggregation and also showed lower site blocking effects, giving more reproducible signals than those from aggregated particles, which compensated for their lower enhancement factor. These results provide a rational basis for selecting enhancing substrates for use in in situ studies, where the further complexity means that it is important to begin with well-understood and controllable enhancing media.


Asunto(s)
Nanopartículas del Metal , Espectrometría Raman , Espectrometría Raman/métodos , Piocianina/química , Biopelículas , Nanopartículas del Metal/química , Pseudomonas aeruginosa/química , Oro/química
6.
J Photochem Photobiol B ; 241: 112671, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36870247

RESUMEN

Antimicrobial resistance is an ever-growing global concern, making the development of alternative antimicrobial agents and techniques an urgent priority to protect public health. Antimicrobial photodynamic therapy (aPDT) is one such promising alternative, which harnesses the cytotoxic action of reactive oxygen species (ROS) generated upon irradiation of photosensitisers (PSs) with visible light to destroy microorganisms. In this study we report a convenient and facile method to produce highly photoactive antimicrobial microparticles, exhibiting minimal PS leaching, and examine the effect of particle size on antimicrobial activity. A ball milling technique produced a range of sizes of anionic p(HEMA-co-MAA) microparticles, providing large surface areas available for electrostatic attachment of the cationic PS, Toluidine Blue O (TBO). The TBO-incorporated microparticles showed a size-dependent effect on antimicrobial activity, with a decrease in microparticle size resulting in an increase in the bacterial reductions achieved when irradiated with red light. The >6 log10Pseudomonas aeruginosa and Staphylococcus aureus reductions (>99.9999%) achieved within 30 and 60 min, respectively, by TBO-incorporated >90 µm microparticles were attributed to the cytotoxic action of the ROS generated by TBO molecules bound to the microparticles, with no PS leaching from these particles detected over this timeframe. TBO-incorporated microparticles capable of significantly reducing the bioburden of solutions with short durations of low intensity red light irradiation and minimal leaching present an attractive platform for various antimicrobial applications.


Asunto(s)
Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/farmacología , Fotoquimioterapia/métodos , Luz , Cloruro de Tolonio/farmacología , Staphylococcus aureus
7.
RSC Adv ; 13(4): 2202-2212, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36741142

RESUMEN

Long-term catheterised individuals are at significant risk of developing catheter-associated urinary tract infections (CAUTIs), with up to 50% of patients experiencing recurrent episodes of catheter encrustation and blockage. Catheter blockage is a result of accumulation of carbonate apatite and struvite formed upon precipitation of ions within urine due to an infection-induced rise in pH. The aim of this study was to investigate the antimicrobial and anti-encrustation activities of tetrasodium ethylenediaminetetraacetic acid (tEDTA) to evaluate its potential efficacy in preventing CAUTIs and catheter blockages. The antimicrobial activity of tEDTA against uropathogens was assessed using time kill assays performed in artificial urine (AU). Crystallisation studies and in vitro bladder model assays were conducted to investigate the effect of tEDTA on struvite crystallisation and catheter blockage. tEDTA displayed bacteriostatic activity against Proteus mirabilis and prevented precipitation of ions in the AU. Crystallisation studies confirmed tEDTA inhibits struvite nucleation and growth via Mg2+ chelation with 7.63 mM tEDTA, equimolar to the concentration of divalent cations in AU, preventing the formation of crystalline deposits and blockage of Foley catheters for ≥168 h. The promising chelating abilities of low tEDTA concentrations could be exploited to inhibit encrustation and blockage of indwelling catheters. The fundamental research presented will inform our future development of an effective tEDTA-eluting catheter coating aimed at preventing catheter encrustation.

8.
Int J Pharm ; 630: 122426, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36427697

RESUMEN

Microwave-induced in situ amorphization is a novel technology for preparing amorphous solid dispersions (ASDs) to address the challenges of their long-term physical stability and downstream processing. To date, only few types of dielectric materials have been reported for microwave-induced in situ amorphization, which restricted the extensive research of this technology. This study aimed to investigate the feasibility and mechanisms of utilizing the non-ionic surfactants, i.e. Kollisolv P124, Kolliphor RH40, D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), Tween (T) 60 (T60), T65, T80 and T85, as plasticizers to facilitate microwave-induced in situ amorphization. It was found that the successful application of surfactants could be related with their low Tm, low Mw and high HLB. Kolliphor RH40 was selected as a typical surfactant due to its excellent dielectric heating ability, plasticizing effect and solubilizing effect when facilitating amorphization. Then, the dissolution-mediated in situ amorphization mechanism was investigated and intuitively demonstrated. For the most promising formulation, i.e. microwaved systems with Korlliphor RH40 at 1.5 (w/w) plasticizer/polymer ratio, a complete and fast in vitro dissolution was observed relative to the untreated systems. In conclusion, non-ionic surfactants had the potential to facilitate microwave-induced in situ amorphization, which provided a new direction in the formulation designation for microwave-able systems.


Asunto(s)
Polímeros , Tensoactivos , Microondas , Solubilidad , Polisorbatos , Plastificantes
9.
Int J Pharm ; 609: 121157, 2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34626795

RESUMEN

Microwave-induced in situ amorphization is an emerging technology to tackle the persistent stability issue of amorphous solid dispersions (ASDs) during manufacture and storage. The aim of this study was to introduce new effective polymeric carriers with diverse properties to microwave-induced in situ amorphization and to better understand their functions in relation to the final dissolution performance of microwaved tablets. Tablets composed of indomethacin (IND) and different polymers were compacted, stored at 75% relative humidity for at least 1 week and microwaved at 1000 W to induce amorphization. A series of polymers, polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios displaying varyingproperties in functional groupratio, hygroscopicity, molecular weight (Mw), and glass transition temperature (Tg) of the polymer were used as model carriers. The results suggested that more than 90% of IND was amorphized after 20 mins microwaving in all 20% (w/w) drug loaded tablets except for IND:PVAc tablets presenting approx. 36% residual crystallinity. Among them, tablets composed of PVP/VA I-335 and PVP K30 achieved complete in situ amorphization upon microwaving. Further analysis indicated that the influencing factors, polymer Mw and Tg of moisture-plasticized polymer, played a major role in microwave-induced in situ amorphization. In in vitro dissolution study, ASDs containing PVP/VA I-535 with moderate hydrophilicity and 0.96 ± 1.92% IND residual crystallinity showed the most rapid and complete drug release among all formulations, presenting the most promising dissolution performance. Further study on the chemical stability of such formulation showed a statistically insignificant decrease of drug content after pre-conditioning and microwaving (P = 0.288 > 0.05).


Asunto(s)
Microondas , Polímeros , Celecoxib , Estabilidad de Medicamentos , Indometacina , Povidona , Solubilidad
10.
Int J Antimicrob Agents ; 58(1): 106360, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33992750

RESUMEN

BACKGROUND: Bacterial spores are an important consideration in healthcare decontamination, with cross-contamination highlighted as a major route of transmission due to their persistent nature. Their containment is extremely difficult due to the toxicity and cost of first-line sporicides. METHODS: Susceptibility of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli to phenothiazinium photosensitizers and cationic surfactants under white- or red-light irradiation was assessed by determination of minimum inhibitory concentrations, minimum bactericidal concentrations and time-kill assays. B. subtilis spore eradication was assessed via time-kill assays, with and without nutrient and non-nutrient germinant supplementation of photosensitizer, surfactant and photosensitizer-surfactant solutions in the presence and absence of light. RESULTS: Under red-light irradiation, >5-log10 colony-forming units/mL reduction of vegetative bacteria was achieved within 10 min with toluidine blue O (TBO) and methylene blue (MB). Cationic surfactant addition did not significantly enhance spore eradication by photosensitizers (P>0.05). However, addition of a nutrient germinant mixture to TBO achieved a 6-log10 reduction after 20 min of irradiation, while providing 1-2 log10 improvement in spore eradication for MB and pyronin Y. CONCLUSIONS: Light-activated photosensitizer solutions in the presence of surfactants and germination-promoting agents provide a highly effective method to eradicate dormant and vegetative bacteria. These solutions could provide a useful alternative to traditional chemical agents used for high-level decontamination and infection control within health care.


Asunto(s)
Bacterias/efectos de los fármacos , Desinfectantes/farmacología , Equipos y Suministros/microbiología , Fármacos Fotosensibilizantes/farmacología , Esporas Bacterianas/efectos de los fármacos , Esterilización/métodos , Tensoactivos/farmacología , Bacillus subtilis/efectos de los fármacos , Infecciones Bacterianas/prevención & control , Infección Hospitalaria/prevención & control , Escherichia coli/efectos de los fármacos , Humanos , Luz , Azul de Metileno/farmacología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pironina/farmacología , Staphylococcus aureus/efectos de los fármacos , Cloruro de Tolonio/farmacología
11.
ACS Biomater Sci Eng ; 7(2): 586-594, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33502846

RESUMEN

Biofouling of surfaces is a major cause of infection and leads to significant patient morbidity and mortality within healthcare settings. With ever-increasing concerns over antibiotic resistance and associated challenges in eradicating surface-attached biofilm communities, efficacious antifouling materials are urgently required. We herein describe the development of an inherently antiadherent polymer system with the capacity for on-demand cleavage of surface-localized surfactant moieties. The nonionic surfactant, Triton X-100, was linked to hydrogel monomers via hydrolytically labile ester bonds. Synthesized copolymers exhibited pH-dependent switching of surfactant release, with elution triggered under the alkaline conditions characteristic of catheter-associated urinary tract infections and subsequently slowed down as the pH decreased, representing eradication of infection. In addition, the materials demonstrated complete resistance to adherence of Staphylococcus aureus following 24 h incubation in infected artificial urine, with reductions in adherence of Proteus mirabilis of up to 89% also observed. This dual-pronged approach with active, infection-responsive cleavage of surfactant to enhance the antiadherent properties of the surfactant-modified surfaces represents a promising self-cleaning strategy without associated concerns over bacterial resistance.


Asunto(s)
Incrustaciones Biológicas , Tensoactivos , Biopelículas , Humanos , Proteus mirabilis , Staphylococcus aureus
12.
J Photochem Photobiol B ; 214: 112098, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33276276

RESUMEN

Infectious disease outbreaks within healthcare facilities can exacerbate patient illness and, in some cases, can be fatal. Contaminated surfaces and medical devices can act as a reservoir for transmission of pathogens and have been linked to the rising incidence of healthcare-acquired infections. Antimicrobial surfaces can reduce microbial contamination and transmission and have emerged as a crucial component in healthcare infection control in recent years. The aim of this study was to manufacture antimicrobial polymer surfaces containing the photosensitiser, toluidine blue O (TBO), using hot-melt extrusion (HME). Several concentrations of TBO were combined with a range of medically relevant polymers via HME. TBO-polymer extrudates displayed no significant differences in thermal properties and surface wettability relative to non-loaded polymers. Minimal leaching of TBO from the surface was confirmed through in vitro release studies. Antibacterial activity was observed to vary according to the polymer and concentration of incorporated TBO, with PEBAX® polymers modified with 0.1% w/w TBO demonstrating promising reductions of >99.9% in viable bacterial adherence of a range of common nosocomial pathogens, including Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter baumannii and Escherichia coli. This study demonstrates the use of HME as a facile alternative method to common encapsulation strategies for the production of light-activated antimicrobial polymer surfaces. This method can be easily translated to large-scale manufacture and, in addition, the polymers constitute promising antimicrobial base materials for the rapidly growing additive manufacturing industries.


Asunto(s)
Antiinfecciosos/química , Portadores de Fármacos/química , Infecciones/terapia , Fármacos Fotosensibilizantes/química , Polímeros/química , Cloruro de Tolonio/química , Antiinfecciosos/farmacología , Ácidos Borónicos/química , Liberación de Fármacos , Humanos , Nylons/química , Fotoquimioterapia , Polímeros/farmacología , Exposición a la Radiación , Propiedades de Superficie , Temperatura de Transición
13.
Pharmaceutics ; 12(7)2020 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-32664477

RESUMEN

The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

14.
Int J Pharm ; 586: 119545, 2020 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-32553496

RESUMEN

Amorphous solid dispersion (ASD) is a formulation strategy extensively used to enhance the bioavailability of poorly water soluble drugs. Despite this, they are limited by various factors such as limited drug loading, poor stability, drug-excipient miscibility and the choice of process platforms. In this work, we have developed a strategy for the manufacture of high drug loaded ASD (HDASD) using hot-melt extrusion (HME) based platform. Three drug-polymer combinations, indomethacin-Eudragit®E, naproxen-Eudragit®E and ibuprofen-Eudragit®E, were used as the model systems. The design spaces were predicted through Flory-Huggins based theory, and the selected HDASDs at pre-defined conditions were manufactured using HME and quench-cooled melt methods. These HDASD systems were also extensively characterised via small angle/wide angle x-ray scattering, differential scanning calorimetry, Infrared and Raman spectroscopy and atomic force microscopy. It was verified that HDASDs were successfully produced via HME platform at the pre-defined conditions, with maximum drug loadings of 0.65, 0.70 and 0.60 w/w for drug indomethacin, ibuprofen and naproxen respectively. Enhanced physical stability was further confirmed by high humidity (95%RH) storage stability studies. Through this work, we have demonstrated that by the implementation of predictive thermodynamic modelling, HDASD formulation design can be integrated into the HME process design to ensure the desired quality of the final dosage form.


Asunto(s)
Ibuprofeno/administración & dosificación , Indometacina/administración & dosificación , Naproxeno/administración & dosificación , Ácidos Polimetacrílicos/química , Química Farmacéutica , Portadores de Fármacos/química , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Excipientes/química , Humedad , Ibuprofeno/química , Indometacina/química , Naproxeno/química , Polímeros/química , Solubilidad , Termodinámica
15.
ACS Omega ; 5(14): 7771-7781, 2020 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-32309685

RESUMEN

Microbial fouling is a costly issue, which impacts a wide range of industries, such as healthcare, food processing, and construction industries, and improved strategies to reduce the impact of fouling are urgently required. Slippery liquid-infused porous surfaces (SLIPSs) have recently been developed as a bioinspired approach to prevent antifouling. Here, we report the development of slippery, superhydrophilic surfaces by infusing roughened poly(vinyl chloride) (PVC) substrates with phosphonium ionic liquids (PILs). These surfaces were capable of reducing viable bacterial adherence by Staphylococcus aureus and Pseudomonas aeruginosa by >6 log10 cfu mL-1 after 24 h under static conditions relative to control PVC. Furthermore, we report the potential of a series of asymmetric quaternary alkyl PILs with varying alkyl chain lengths (C4-C18) and counteranions to act as antimicrobial agents against both Gram +ve and Gram -ve bacteria and illustrate their potential as antimicrobial alternatives to traditional fluorinated lubricants commonly used in the synthesis of SLIPSs.

16.
ACS Appl Bio Mater ; 3(3): 1385-1393, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35021631

RESUMEN

Poly(vinyl chloride) (PVC) biomaterials perform a host of life-saving and life-enhancing roles when employed as medical devices within the body. High frictional forces between the device surface and interfacing tissue can, however, lead to a host of complications including tissue damage, inflammation, pain, and infection. We herein describe a versatile surface modification method using multifunctional hydrogel formulations to increase lubricity and prevent common device-related complications. In a clinically relevant model of the urinary tract, simulating the mechanical and biological environments encountered in vivo, coated candidate catheter surfaces demonstrated significantly lower frictional resistance than uncoated PVC, with reductions in coefficient of friction values of more than 300-fold due to hydration of the surface-localized polymer network. Furthermore, this significant lubrication capacity was retained following hydration periods of up to 28 days in artificial urine at pH 6 and pH 9, representing the pH of physiologically normal and infected urine, respectively, and during 200 repeated cycles of applied frictional force. Importantly, the modified surfaces also displayed excellent antibacterial activity, which could be facilely tuned to achieve reductions of 99.8% in adherence of common hospital-acquired pathogens, Staphylococcus aureus and Proteus mirabilis, relative to their uncoated counterparts through incorporation of chlorhexidine in the coating matrix as a model antiseptic. The remarkable, and pH-independent, tribological performance of these lubricious, antibacterial, and highly durable surfaces offers exciting promise for use of this PVC functionalization approach in facilitating smooth and atraumatic insertion and removal of a wide range of medical implants, ultimately maintaining user health and dignity.

17.
Chemistry ; 26(16): 3555-3563, 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-31742800

RESUMEN

The crystallization of magnesium ammonium phosphate hexahydrate (struvite) often occurs under conditions of fluid flow, yet the dynamics of struvite growth under these relevant environments has not been previously reported. In this study, we use a microfluidic device to evaluate the anisotropic growth of struvite crystals at variable flow rates and solution supersaturation. We show that bulk crystallization under quiescent conditions yields irreproducible data owing to the propensity of struvite to adopt defects in its crystal lattice, as well as fluctuations in pH that markedly impact crystal growth rates. Studies in microfluidic channels allow for time-resolved analysis of seeded growth along all three principle crystallographic directions and under highly controlled environments. After having first identified flow rates that differentiate diffusion and reaction limited growth regimes, we operated solely in the latter regime to extract the kinetic rates of struvite growth along the [100], [010], and [001] directions. In situ atomic force microscopy was used to obtain molecular level details of surface growth mechanisms. Our findings reveal a classical pathway of crystallization by monomer addition with the expected transition from growth by screw dislocations at low supersaturation to that of two-dimensional layer generation and spreading at high supersaturation. Collectively, these studies present a platform for assessing struvite crystallization under flow conditions and demonstrate how this approach is superior to measurements under quiescent conditions.

18.
ACS Appl Mater Interfaces ; 11(30): 27269-27278, 2019 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-31260238

RESUMEN

Through a nature-inspired layer-by-layer assembly process, we developed a unique multifunctional tissue scaffold that consists of porous polyurethane substrate and nanoscale chitosan/graphene oxide hybrid coating. Alternative layers of drug-laden chitosan and graphene oxide nanosheets were held together through strong electrostatic interaction, giving rise to a robust multilayer architecture with control over structural element orientation and chemical composition at nanoscale. Combined pH-controlled co-delivery of multiple therapeutic agents and photothermal therapy has been achieved by our scaffold system. The new platform technology can be generalized to produce other tissue scaffold systems and may enable potential multimodal therapeutic applications such as bone cancer managements.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Quitosano/química , Materiales Biocompatibles Revestidos/química , Ingeniería de Tejidos , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/uso terapéutico , Liberación de Fármacos/efectos de los fármacos , Durapatita/química , Grafito/química , Humanos , Concentración de Iones de Hidrógeno , Fototerapia , Porosidad , Andamios del Tejido/química
19.
Chem Commun (Camb) ; 55(12): 1754-1757, 2019 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-30664130

RESUMEN

Two lanthanide luminescent naphthyl-dipicolinic amide (dpa) methacrylate monomers for the synthesis of grafted supramolecular co-polymer gels (hydrogels), and their use as additional crosslinks in robust covalently cross-linked HEMA hydrogels is presented; the results demonstrate the importance of the ligand symmetry for the Eu(iii) emission from the hydrogels.

20.
Proc Inst Mech Eng H ; 233(1): 84-90, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29393009

RESUMEN

Lubricity is a key property of hydrophilic-coated urinary catheter surfaces. In vitro tests are commonly employed for evaluation of surface properties in the development of novel catheter coating technologies; however, their value in predicting the more subjective feeling of lubricity requires validation. We herein perform a range of in vitro assessments and human organoleptic studies to characterise surface properties of developmental hydrophilic coating formulations, including water wettability, coefficient of friction, dry-out kinetics and lubricity. Significant reductions of up to 40% in the contact angles and coefficient of friction values of the novel coating formulations in comparison with the control poly(vinylpyrrolidone)-coated surfaces were demonstrated during quantitative laboratory assessments. In contrast, no significant differences in the more subjective feeling of lubricity between the novel formulations and the control-coated surfaces were observed when formulations were haptically assessed by the techniques described herein. This study, importantly, highlights the need for optimisation of in vitro and human haptic assessments to more reliably predict patient preferences.


Asunto(s)
Fricción , Ensayo de Materiales/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales/instrumentación , Propiedades de Superficie , Catéteres Urinarios
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