Physicochemical characterization of bioactive polyacrylic acid organogels as potential antimicrobial implants for the buccal cavity

This study describes the formulation and physicochemical characterization of poly(acrylic acid) (PAA) organogels, designed as bioactive implants for improved treatment of infectious diseases of the oral cavity. Organogels were formulated containing a range of concentrations of PAA (3-10% w/w) and metronidazole (2 or 5% w/w, representing a model antimicrobial agent) in different nonaqueous solvents, namely, glycerol (Gly), polyethylene glycol (PEG 400), or propylene glycol (PG). Characterization of the organogels was performed using flow rheometry, compressional analysis, oscillatory rheometry, in vitro mucoadhesion, moisture uptake, and drug release, methods that provide information pertaining to the nonclinical and clinical use of these systems. Increasing the concentration of PAA significantly increased the consistency, compressibility, storage modulus, loss modulus, dynamic viscosity, mucoadhesion, and the rate of drug release. These observations may be accredited to enhanced molecular polymer entanglement. In addition, the choice of solvent directly affected the physicochemical parameters of the organogels, with noticeable differences observed between the three solvents examined. These differences were accredited to the nature of the interaction of PAA with each solvent and, importantly, the density of the resultant physical cross-links. Good correlation was observed between the viscoelastic properties and drug release, with the exception of glycerol-based formulations containing 5 and 10% w/w PAA. This disparity was due to excessive swelling during the dissolution analysis. Ideally, formulations should exhibit controlled drug release, high viscoelasticity, and mucoadhesion, but should flow under minimal stresses. Based on these criteria, PEG 400-based organogels composed of 5% or 10% w/w PAA exhibited suitable physicochemical properties and are suggested to be a potentially interesting strategy for use as bioactive implants designed for use in the oral cavity. © 2008 American Chemical Society.

Persistence of antimicrobial activity through sustained release of triclosan from pegylated silicone elastomers

Microbial adhesion to silicone elastomer biomaterials is a major problem often resulting in infection and medical device failure. Several strategies have been employed to modulate eukaryotic cell adhesion and to hamper bacterial adherence to polymeric biomaterials. Chemical modification of the surface by grafting of polyethylene glycol (PEG) chains or the incorporation of non-antibiotic antimicrobial agents such as triclosan into the biomaterial matrix may reduce bacterial adhesion. Here, such strategies are simultaneously applied to the preparation of both condensation-cure and addition-cure silicone elastomer systems, seeking a sustained release antimicrobial device biomaterial. The influence of triclosan incorporation and degree of pegylation on antimicrobial release, surface microbial adherence and persistence (Escherichia coli and Staphylococcus epidermidis) were evaluated in vitro. Non-pegylated silicone elastomers provided an increased percentage release of triclosan extending over a relatively short duration (99% release by day 64) compared with their pegylated (4% w/w) counterparts (65% and 72% release by day 64, for condensation and addition-cure systems respectively). Viable E. coli adherence to a non-pegylated silicone elastomer containing 1% w/w triclosan was reduced by over 99% after 24 h compared to the non-pegylated silicone elastomer containing no triclosan. No viable S. epidermidis adhered to any of the triclosan-loaded (>0.1% w/w) formulations other than the control. Persistence of the antimicrobial activity of the triclosan-loaded pegylated silicone elastomers continued for at least 70 days compared to the triclosan-loaded non-pegylated elastomers (at least 49 days). Understanding how PEG affects the release of triclosan from silicone elastomers may prove useful in the development of a biomaterial providing prolonged, effective antimicrobial activity.

Physicochemical Characterization of Poly(ethylene glycol) Plasticized Poly(methyl vinyl ether-co-maleic acid) Films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade

An examination of the rheological and mucoadhesive properties of poly(Acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity

This study examined the rheological/mucoadhesive properties of poly (acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G '') moduli of organogels as a function of frequency was minimal, G '' was greater than G '' (at all frequencies), and the loss tangent <1, indicative of gel behavior. Organogels prepared using EG, PG, and 1,3-propanediol (1,3-PD) exhibited similar flow/viscoelastic properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity.

Synthesis of a neodymium-quinolate complex for near-infrared electroluminescence applications

A structurally pure, near-infrared emissive Nd-(5,7-dichloro-8-hydroxyquinoline)4 tetrakis complex has been synthesized. When incorporated as a dopant in the blue emissive, hole conducting polymer poly(N-vinylcarbazole), PVK, sensitized neodymium ion emission was observed following photo-excitation of the polymer host. OLED devices were fabricated by spin-casting layers of the doped polymer onto glass/indium tin oxide (ITO)/3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates. An external quantum efficiency of 1 x 10(-3)% and a near-infrared irradiance of 2.0 nW/mm(2) at 25 mA/mm(2) and 20 V was achieved using glass/ITO/PEDOT/ PVK:Nd-(5,7-dichloro-8-hydroxyquinoline)(4)/Ca/Al devices. (C) 2007 Elsevier B.V. All rights reserved.

Application of poly(ethylene glycol)-based aqueous biphasic systems as reaction and reactive extraction media

Poly(ethylene glycol)-based aqueous biphasic systems (PEG-ABSs) have been investigated as tunable reaction media, in the example presented here, to control the oxidation of cyclohexene to adipic acid with hydrogen peroxide. The production of adipic acid was found to increase from the monophasic to the biphasic regimes, was greatest at short tie-line lengths (close to the system's critical point), and demonstrates how control of the ABS media, through changes in system composition, PEG, salt, and tie-line length, can be used to readily tune and control reactivity and product isolation in these aqueous biphasic reactive extraction systems. Challenges in using this system, including possible oxidation reactions of the PEG-OH end groups, are also discussed.

Gelation of ionic liquids using a cross-linked poly(ethylene glycol) gel matrix

Conductive ionic liquid -poly(ethylene glycol) (IL-PEG) gels have been prepared by gelation of the hydrophobic ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [(C(6)mim] [NTf2]) by the cross-linking reaction of disuccinimidylpropyl PEG monomers with four-arm tetraamine PEG cross-linkers. This is the first time that a crosslinked PEG matrix, such as this, has been used to gel nonaqueous solvents. Initial studies screening other ionic liquids as solvents indicate that the gelation of the ionic liquid is both cation and anion dependent with smaller, coordinating cations disrupting or preventing gel formation.

Near infrared electroluminescence from neodymium complex-doped polymer light emitting diodes

Organic light emitting diode devices employing organometallic Nd(9-hydroxyphenalen-1-one)(3) complexes as near infrared emissive dopants dispersed within poly(N-vinylcarbazole) (PVK) host matrices have been fabricated by spin-casting layers of the doped polymer onto glass/indium tin oxide (ITO)/3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates. Room temperature electroluminescence, centered at similar to 1065 nm. was observed from devices top contacted by evaporated aluminum or calcium metal cathodes and was assigned to transitions between the F-4(3/2) -> I-4(11/2) levels of the Nd3+ ions. In particular, a near infrared irradiance of 8.5 nW/mm(2) and an external quantum efficiency of 0.007% was achieved using glass/ITO/PEDOT/PVK:Nd(9-hydroxyphenalen-1-one)(3)/Ca/Al devices. (c) 2005 Elsevier B.V. All rights reserved.

Narrow bandwidth red electroluminescence from solution-processed lanthanide-doped polymer thin films

Narrow bandwidth red electroluminescence from OLED devices fabricated using a simple solution-based approach is demonstrated. A spin-casting method is employed to fabricate organic light emitting diode (OLED) devices comprising a poly(N-vinylcarbazole) (PVK) host matrix doped with a europium beta-diketonate complex, Eu(dbM)(3)(Phen) (dibenzoylmethanate, dbm; 1,10-phenanthroline, Phen) on glass/ indium tin oxide (ITO)/3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates. Saturated red europium ion emission, based on the (5)Do ->F-7(2) transition, is centered at a wavelength of 612 nm with a full width at half maximum of 3.5 rim. A maximum external quantum efficiency of 6.3 x 10(-2) cd/A (3.1 X 10(-2)%) and a maximum luminance of 130 cd/M-2 at 400 mA/cm(2) and 25 V is measured for ITO/PEDOT/PVK:Eu(dbM)3(Phen)/Ca/Al devices. This measured output luminance is comparable to that of devices fabricated using more sophisticated small molecule evaporation techniques. (c) 2005 Elsevier B.V All rights reserved.