Microfibrillated cellulose films containing chitosan and tannic acid for wound healing applications.

The effectiveness of tannic acid as antimicrobial and wound healing for burns have been shown for a century; however, uncontrolled target dosage may result in undesirable side-effects. Remarkably, tannic acid polyphenols compounds crosslinked with polymeric materials produce a strong composite containing the beneficial properties of this tannin. However, investigation of the crosslink structure and its antibacterial and regenerative properties are still unknown when using nanocellulose by mechanical defibrillation; additionally, due to the potential crosslink structure with chitosan, its structure can be complex. Therefore, this work uses bleach kraft nanocellulose in order to investigate the effect on the physical and regenerative properties when incorporated with chitosan and tannic acid. This film results in increased rigidity with a lamellar structure when incorporated with tannic acid due to its strong hydrogen bonding. The release of tannic acid varied depending on the structure it was synthesised with, whereas with chitosan it presented good release model compared to pure cellulose. In addition, exhibiting similar thermal stability as pure cellulose films with antibacterial properties tested against S. aureus and E. coli with good metabolic cellular viability while also inhibiting NF-κB activity, a characteristic of tannic acid.

Co-axial electrosprayed RAD001-loaded polycaprolactone/polyvinyl alcohol core-shell particles for treating pediatric brain tumours.

Core-shell particles composed of polycaprolactone/polyvinyl alcohol (PCL/PVA) with pH sensitive properties were successfully fabricated by co-axial electrospraying in which PVA and PCL formed the shell and core layers respectively. The core-shell structure was confirmed by FTIR, DSC and SEM analysis. No chemical interaction between PVA and PCL core-shell were observed in the FTIR analysis. The RAD001 loaded core-shell particles showed a sustained and pH dependent drug release and was assayed via our previously developed HPLC method. After indirect treatment of the PF-A cells with the core-shell particles for 24 h and 5 days a decrease in cell viability was observed. Additionally, a comparison was made with our previously developed nanoparticles containing 2 %PVA-14 %SOL®-0.6 % RAD001, for the cell viability study on ependymoma. Our findings show that optimised core-shell particles exerted a significant effect for the 24 h and 5 day treatment however further studies are required to ensure toxicity of the control core-shell particles with no drug is reduced. In comparison, the 2 %PVA-14 %SOL®-0.6 %RAD001 uniaxial electrosprayed nanoparticles also exerted a toxicity effect decreasing cell viability with no toxicity observed for the control nanoparticles as well. Such pH-sensitive core-shell particles, which can degrade effectively in either acidic or neutral condition, have great potential for application in the biomedical field.

Design, development and in vitro quantification of novel electrosprayed everolimus-loaded Soluplus®/Polyvinyl alcohol nanoparticles via stability-indicating HPLC method in cancer therapy.

Everolimus (RAD001) a mammalian target of rapamycin has been hampered by poor solubility, affecting its dissolution rate, a relationship that extends to low bioavailability. Nanoparticles (NP) based on Soluplus (SOL®) and Polyvinyl alcohol (PVA) was fabricated by electrospraying (ES) for the delivery of RAD001 to improve anti-tumour efficacy. Electrospraying with established experimental conditions produced PVA-SOL®-RAD001 NP with 71 nm mean diameter, smaller particle size distribution and >90 % encapsulation efficiency. Various polymer-drug concentrations exposed to various freeze-thaw (F/T) cycles were studied for NP optimisation and to enhance its mechanical properties. The optimised NP formulation demonstrated complete encapsulation as well as a sustained and pH dependent drug release profile for in vitro release test. In addition, to specifically study the degradation profile of RAD001 and to quantify RAD001 in the fabricated NP, a new HPLC method was developed and validated. The purpose and novelty of the HPLC method was also to ensure that RAD001 can be detected at low amounts where other conventional characterisation methods are unable to detect. The developed HPLC method was accurate, precise, robust and sensitive with LOD and LOQ values of 4.149 and 12.575 µg/mL. In conclusion, the novel developed HPLC system can be applied for the quantification of different chemotherapeutic agents and the novel electrosprayed hydrogel NP is a potential drug delivery system to increase solubility and bioavailability of RAD001 in cancer therapy.

Nanofibrillated cellulose originated from Rhododendron ponticum to produce scaffolds using 3D printing for biomedical applications.

Rhododendron ponticum is an invasive species that spreads rapidly and is described as one of the biggest threats to peatlands in Ireland. This study offers an innovative approach to utilizing Rhododendron waste. Initially, sawdust was submitted to a bleaching treatment and the nanofibrillated cellulose (NFC) was obtained using two different methods: ultra-fine friction grinding and twin-screw extrusion with the assistance of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) pre-treatment. The samples processed through twin-screw extrusion exhibited the presence of NFC at five intervals, as confirmed by TEM analysis. However, these samples displayed a higher diameter deviation compared to those processed through grinding alone. Notably, after 20 extrusion steps, the NFC diameter became more uniform, reaching approximately 35 nm. Sedimentation tests showed that extrusion produced more homogeneous cellulose size than the grinder method. However, FTIR characterization for the samples showed a unique band related to C-O-C glycosidic linkage. The results showed that grinding breaks these groups resulting in crystallinity values lower than extrusion, 50 % compared 60 %. Therefore, NFC with 20 steps by grinding was blended with polycaprolactone to produce a 3D scaffold using a 3D printer at different ratios of 1-5 % addition. The effect of 1 % of NFC was unique showing significant enhanced mechanical properties compared to pure polycaprolactone (PCL), additionally, the NFC does not exhibit toxicity so these materials show promise for biomedical applications.

Self-Photopolymerizable Hydrogel-Ceramic Composites with Scavenger Properties.

The photocatalytic behaviours of semiconductive ceramic nanoparticles such as TiO2, ZnO, Fe2O3, and Fe3O4, have been extensively studied in photocatalysis and photopolymerization, due to their ability to produce radical species under ultraviolet-visible light, and even in dark conditions. In addition, in the form of microparticles, TiO2 and its Magnéli phases are capable of neutralizing radical species, and a heterogeneous catalytic process has been suggested to explain this property, as it is well known as scavenging activity. Thus, in this study, we demonstrate that these ceramic powders, in the form of microparticles, could be used as photoinitiators in UV polymerization in order to synthesize a hydrogel matrix. Them, embedded ceramic powders could be able to neutralize radical species of physiological media once implanted. The hydrogel matrix would regulate the exchange of free radicals in any media, while the ceramic particles would neutralize the reactive species. Therefore, in this work, the scavenger activities of TiO2, ZnO, Fe2O3, and Fe3O4 microparticles, along with their photoinitiation yield, were evaluated. After photopolymerization, the gel fraction and swelling behaviour were evaluated for each hydrogel produced with different ceramic initiators. Gel fractions were higher than 60%, exhibiting variation in their scavenging activity. Therefore, we demonstrate that ceramic photoinitiators of TiO2, ZnO, Fe2O3, and Fe3O4 can be used to fabricate implantable devices with scavenger properties in order to neutralize radical species involved in inflammatory processes and degenerative diseases.

Characterization of Gels and Films Produced from Pinhão Seed Coat Nanocellulose as a Potential Use for Wound Healing Dressings and Screening of Its Compounds towards Antitumour Effects.

The reuse of agro-industrial waste assumes great importance today. Pinhão is the seed of Araucaria angustifolia, which is native to the mountains of southern Brazil, Paraguay, and Argentina. The coat is a by-product of this seed and is rich in phenolic compounds. The present study aimed to use the residue as a precursor material for the production of nanocellulose through the mechanical defibrillation process and perform the characterization of the films and the gel to investigate the effect on the physical and regenerative properties when incorporated with polyvinyl alcohol (PVA). The modulus of elasticity was higher when the MFC of pinhão was added to the PVA. Film and gel had their cytotoxicity tested by MTT assay using 3T3 fibroblast and Schwann cancer cells, and a migration assay was also performed using the scratch test on HaCat keratinocyte cells. For the scratch test, film and gel samples with low concentration presented a complete scratch closure in 72 h. Molecular docking was performed and quercetin had the ideal interaction score values, so it was used with the PACAP protein which presented a slightly moderate interaction with the protein synthesis of Schwann cells, presenting compactness of the compound after 14 ns.

Development, Characterization and Cell Viability Inhibition of PVA Spheres Loaded with Doxorubicin and 4'-Amino-1-Naphthyl-Chalcone (D14) for Osteosarcoma.

Chalcones (1,3-diaryl-2-propen-1-ones) are naturally occurring polyphenols with known anticancer activity against a variety of tumor cell lines, including osteosarcoma (OS). In this paper, we present the preparation and characterization of spheres (~2 mm) from polyvinyl alcohol (PVA) containing a combination of 4'-Amino-1-Naphthyl-Chalcone (D14) and doxorubicin, to act as a new polymeric dual-drug anticancer delivery. D14 is a potent inhibitor of osteosarcoma progression and, when combined with doxorubicin, presents a synergetic effect; hence, physically crosslinked PVA spheres loaded with D14 and doxorubicin were prepared using liquid nitrogen and six freeze-thawing cycles. Physical-chemical characterization using a scanning electron microscope (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) presented that the drugs were incorporated into the spheres via weak interactions between the drugs and the polymeric chains, resulting in overall good drug stability. The cytotoxicity activity of the PVA spheres co-encapsulating both drugs was tested against the U2OS human osteosarcoma cell line by 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay, and compared to the spheres carrying either D14 or doxorubicin alone. The co-delivery showed a cytotoxic effect 2.6-fold greater than doxorubicin alone, revealing a significant synergistic effect with a coefficient of drug interaction (CDI) of 0.49. The obtained results suggest this developed PVA sphere as a potential dual-drug delivery system that could be used for the prominent synergistic anticancer activity of co-delivering D14 and doxorubicin, providing a new potential strategy for improved osteosarcoma treatment.

Yerba Mate Extract in Microfibrillated Cellulose and Corn Starch Films as a Potential Wound Healing Bandage.

Microfibrillated cellulose films have been gathering considerable attention due to their high mechanical properties and cheap cost. Additionally, it is possible to include compounds within the fibrillated structure in order to confer desirable properties. Ilex paraguariensis A. St.-Hil, yerba mate leaf extract has been reported to possess a high quantity of caffeoylquinic acids that may be beneficial for other applications instead of its conventional use as a hot beverage. Therefore, we investigate the effect of blending yerba mate extract during and after defibrillation of Eucalyptus sp. bleached kraft paper by ultrafine grinding. Blending the extract during defibrillation increased the mechanical and thermal properties, besides being able to use the whole extract. Afterwards, this material was also investigated with high content loadings of starch and glycerine. The results present that yerba mate extract increases film resistance, and the defibrillated cellulose is able to protect the bioactive compounds from the extract. Additionally, the films present antibacterial activity against two known pathogens S. aureus and E. coli, with high antioxidant activity and increased cell proliferation. This was attributed to the bioactive compounds that presented faster in vitro wound healing, suggesting that microfibrillated cellulose (MFC) films containing extract of yerba mate can be a potential alternative as wound healing bandages.

Effect of cellulose size-concentration on the structure of polyvinyl alcohol hydrogels.

Microfibrillated cellulose as a reinforcement agent has been investigated extensively due to their unique characteristics, which can reorder the structure of polymers and hydrogels leading to improved mechanical properties with minimal disadvantages in terms of the targeted original applications. However, effect of using a macro- to a micro-fibrillated cellulose onto polyvinyl alcohol hydrogels is still unknown, because of the unique ability for both to be produced as hydrogels from freeze-thawing mechanisms - hydrogen bonding - there is a potential synergism. Therefore, macro and microfibrillated kraft bleached paper was synthesised at various concentrations on polyvinyl alcohol hydrogels. The overall effect presented a strong interaction between both compounds but it was increased with macrofibrillated cellulose. Increase in crystallinity was also observed with a macro-sized fibre without variation on tensile elastic modulus but an overall improvement was perceived on thermal properties and a slower swelling rate with a microfibrillated cellulose.

A tough and novel dual-response PAA/P(NiPAAM-co-PEGDMA) IPN hydrogels with ceramics by photopolymerization for consolidation of bone fragments following fracture.

In this work, a novel dual-response hydrogel for enhanced bone repair following multiple fractures was investigated. The conventional treatment of multiple bone fracture consists on removing smaller bone fragments from the body in a surgery, followed by the fixation of the bone using screws and plates. This work proposes an alternative for this treatment via in situ UV-initiated radical polymerization of a novel IPN hydrogel composed of PAA/P(NiPAAM-co-PEGDMA) incorporated with ceramic additives. The influence of different additives on mechanical properties and sensitivity of the polymer, as well as the prepolymer mixture, were investigated in order to analyse the suitability of the composites for bone healing applications. This material exhibited an interpenetrating network, confirmed by FTIR, with ceramics particles dispersed in between the polymer network. These structures presented high strength by tensile tests, sensitivity to pH and temperature and a decrease on Tg values of NiPAAm depending on the amount of PEGDMA and ceramics added; although, the addition of ceramics to these composites did not decrease their stability drastically. Finally, cytotoxicity tests revealed variations on the toxicity, whereas the addition of TCP presented to be non-toxic and that the cell viability increased when ceramics additives were incorporated into the polymeric matrix with an increased reporter activity of NF-κB, associated with aiding fibroblast adhesion. Hence, it was possible to optimise feedstock ratios to increase the applicability of the prepolymer mixture as a potential treatment of multiple fractures.

Characterisation and controlled drug release from novel drug-loaded hydrogels.

Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly(N-isopropylacrylamide)-poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for 'smart' drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.

Preparation of a novel freeze thawed poly(vinyl alcohol) composite hydrogel for drug delivery applications.

We describe a drug delivery system based on a physically cross-linked poly(vinyl alcohol) (PVA) hydrogel for the release of Theophylline (TH). A composite was created by freezing an aqueous solution of PVA/NaOH onto a PVA/poly(acrylic acid) substrate. This formed a strong interface and demonstrated greater physical strength than the hydrogel alone. Such systems have potential for a variety of localised controlled drug delivery applications, for example, as coatings for implantable devices. Importantly, the results suggest that a versatile synthetic platform is possible that may provide different functional materials or combination of such. The resultant samples were characterised using optical microscopy, modulated differential scanning calorimetry (MDSC) and dissolution testing. The microstructure of the gels was examined using micro-thermal analysis (microTA) which is a combination of atomic force microscopy and thermal analysis. TH was found to have an effect on the crystalline structure and dissolution showed a Fickian release, suggesting that swelling and crystallinity were the controlling mechanisms.

Extraction Method Plays Critical Role in Antibacterial Activity of Propolis-Loaded Hydrogels.

Extracted propolis has been used for a long time as a remedy. However, if the release rate of propolis is not controlled, the efficacy is reduced. To overcome this issue, extracted propolis was added to a cryogel system. Propolis collected from southern Brazil was extracted using different methods and loaded at different concentrations into polyvinyl alcohol (PVA) and polyacrylic acid hydrogels as carrier systems. The material properties were investigated with a focus on the propolis release profiles and the cryogel antibacterial properties against 4 different bacteria, namely: Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas putida. Swelling studies indicated that the swelling of the hydrogel was inversely related to propolis content. In addition, propolis release studies indicated a decreased release rate with increased propolis loading. PVA and PVA/polyacrylic acid-loaded propolis were effective against all 4 bacteria studied. These results indicate that the efficacy of propolis can be enhanced by incorporation into hydrogel carrier systems and that hydrogels with higher concentrations of propolis can be considered for use as bactericide dressing.

Development and characterisation of an agar--polyvinyl alcohol blend hydrogel.

Numerous authors have reported on hydrogel technologies providing products suitable for applications in biomedical, personal care as well as in nano-sensor applications. Hydrogels fabricated from single polymers have been extensively investigated. However, in many cases a single polymer alone cannot meet divergent demands in terms of both properties and performance. In this work, hydrogels were prepared by physically blending the natural polymer agar with polyvinyl alcohol in varying ratios to produce a new biosynthetic polymer applicable for a variety of purposes. Hydrogen bonding was observed to take place between the polyvinyl alcohol and the agar molecules in the composite materials leading to changes in the thermal, mechanical and swelling characteristics of the composite hydrogels. The composite hydrogels exhibited a slightly higher melting temperature than pure agar (116.81 degrees C). Irreversible compressive damage was found to occur at lower strain levels during compression testing of the dehydrated samples consisting of higher PVOH concentrations. Rheological analysis of hydrated sample revealed G' values of between 5000 and 10,000 Pa for the composite blends, with gels containing higher PVOH percentages exhibiting poorer mechanical strength.

The synthesis of novel pH-sensitive poly(vinyl alcohol) composite hydrogels using a freeze/thaw process for biomedical applications.

Physically cross-linked hydrogels composed of 75% poly(vinyl alcohol) PVA and 25% poly(acrylic acid) were prepared by a freeze/thaw treatment of aqueous solutions. Between 0.5 and 1wt% of aspirin was incorporated into the systems. The purpose of the research was the development of a novel pH-sensitive hydrogel composite for the delivery of aspirin to wounds. Extensive research has being conducted on freeze/thaw poly(vinyl alcohol) hydrogels for use in active pharmaceutical ingredient (API) delivery. However very little research has been reported on the effects of an API on the overall properties of a freeze/thaw hydrogel. From the rheological analysis undertaken it was apparent that aspirin has a limiting effect on the formation of hydrogen bonding leading to hydrogels with reduced mechanical strength. To counteract this, a novel hydrogel system was developed encompassing a reinforcing film in the centre of the hydrogels. Freezing profiles were obtained to gain a better knowledge of the freezing behaviour of the hydrogels during the formation stage. Thermograms obtained from modulated differential scanning calorimetry (MDSC) indicated that the aspirin lowered the glass transition temperatures (T(g)) of the constituent polymers. The pH-sensitive nature of the hydrogels was apparent from solvent uptake studies carried out. Increasing alkaline media led to a greater degree of swelling due to increased ionisation of PAA. The hydrogels exhibited non-Fickian release kinetics. The release rates were relatively slow with total release achieved at between 30 and 40 h. The quantity of drug incorporated was found to influence the release rates considerably.

Investigation of a novel freeze-thaw process for the production of drug delivery hydrogels.

Poly(vinyl alcohol) (PVA) is a water-soluble, biocompatible and biodegradable polymer, which has been widely applied in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of PVA and comprising a blend of poly(vinyl alcohol) (PVA) with different concentrations of HCl, NaOH and NaCl are prepared by a freezing/thawing treatment of aqueous solutions. The structure and complexation of the electrolytes were studied by Fourier transform infrared (FTIR) spectroscopy. The mechanical properties were investigated using rheometery and the thermal transitions of the hydrogels were examined by modulated differential scanning calorimetry (MDSC). Freeze/thawed PVA gels containing NaOH showed overall enhanced swelling with increased mechanical strength over traditional gels prepared by chemical or irradiative crosslinking techniques. These novel physically cross-linked hydrogels show promise for a variety of biomedical and drug delivery applications.