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  • 1
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective To investigate the efficacy of a novel method for the treatment of cervical intraepithelial neoplasia. A cytotoxic drug delivery system using a bilaminar bioadhesive polymeric film was applied directly to the cervix. This cytotoxic drug delivery system allowed the dose, the site and the duration of application of the cytotoxic drug (5-fluorouracil) to be controlled.Design A prospective, double-blind randomised controlled trial.Setting The Departments of Obstetrics and Gynaecology and Pathology of Belfast City Hospital and The Queen's University of Belfast, and the Department of Pharmacy of The Queen's University of Belfast.Participants One hundred and four patients who had been referred to the colposcopy outpatient clinic because of abnormal cervical cytology were recruited into the trial. They were assessed colposcopically and biopsies for histopathology were obtained. Only patients with cervical intraepithelial neoplasia lesions Grades 1 and 2 were recruited.Interventions All patients were re-assessed one, three, and six months after application of the cytotoxic drug delivery system by colposcopy. Clinical endpoints were noted.Main outcome measures Pre-treatment histopathological biopsy results were compared with those obtained after treatment.Results The cytotoxic drug delivery system fulfilled the requirements for treatment of cervical intraepithelial neoplasia without causing any architechtural damage, but the chemotherapeutic agent, 5-fluorouracil, did not provide effective treatment of disease.Conclusions This study showed that the delivery system was effective, and further studies using this mechanism are now possible.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Aminolevulinic acid (ALA) is a charged, hydrophilic molecule that penetrates poorly through cellular structures. This property has been implicated in the poor clinical response of non-superficial basal cell carcinomas (BCCs) to photodynamic therapy (PDT). Release of ALA hydrochloride from a 20% w/w formulation was found to be incomplete and that approximately 36.8% of the total dose is released during the application period of 4 h. Using scintillation spectroscopy and a precise tissue sectioning protocol, it was demonstrated that depths of penetration of at least 2 mm from the lesion surface had been reached. Using cumulative stratal ALA concentrations, it was found that 10% of the total applied dose permeated into the lesion. In spite of this, comparisons drawn with photodynamic concentrations used in tissue culture work reported elsewhere revealed that estimations of the ALA concentration at 2 mm were sufficient to elicit a possible therapeutic response. Results from this work question the reasons given for poor outcomes of PDT in nodular BCC based solely on depth as a hindering factor.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: cervical intraepithelial neoplasia ; bioadhesive ; 5-fluorouracil ; liquid scintillation spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The potential use of bioadhesive technology for the treatment of cervical intraepithelial neoplasia was investigated. A cervical patch was designed containing 5-fluorouracil in a bioadhesive matrix and polyvinyl chloride as the backing layer. The concentration of 5-fluorouracil at specified tissue depths from the cervical surface was determined in vitro in relation to the ability of the drug to reach precancerous foci in cervical crypts up to 4 mm below the tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5-fluorouracil-6-3H and subsequently sectioned to obtain tissue slices at different depths. The concentration of 5-fluorouracil was determined by liquid scintillation spectrometry. Drug penetration into cervical tissue exceeded a depth of 5.5 mm. Furthermore, the concentration in the tissue depended on the drug loading in the patch. Patches containing 10 and 20 mg of 5-fluorouracil produced a linear drug gradient that was established after a 4 hour application of the patch and persisted over 24 hours. However, patches containing 3.5 mg of 5-fluorouracil displayed signs of drug exhaustion after 24 hours. The penetration characteristics of 5-fluorouracil through cervical tissue using the cervical patch delivery system were sufficiently favourable to warrant further clinical investigations.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Keywords: autoradiography ; bioadhesive ; cervical intraepithelial neoplasia ; 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The distribution of 5-fluorouracil through cervical tissue has been assessed following the in vitro application of a bioadhesive patch to excised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-3H and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned perpendicular to the plane of the applied patch and the autoradiographic image developed by placing a frozen tissue slice on Hyperfilm with subsequent instant thawing and refreezing, the resulting bilayer being maintained at −18°C for 24 hours. The developed image was analysed by scanning densitometry and raster scans were visualised with three-dimensional contouring software. The autoradiograms showed darker areas surrounding tissue ducts, suggesting that 5-FU was spilling from the lumen into the surrounding stroma. Transport of 5FU via aqueous channels may thus make an important contribution to the rapid penetration of the drug through the cervical stroma. Three-dimensional autoradiographic images showed that, for a 4-hour patch application, there were areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervical crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-904X
    Keywords: periodontal diseases ; bioadhesive semi-solids ; tetracycline ; zero-order release ; texture profile analysis ; syringeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases. Methods. Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37°C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance. Results. Tetracycline release from all formulations was zero-order for 24–54 h and ranged from 1.59 ± 0.20 to 15.80 ± 0.50 mg h−1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components. Conclusions. The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-904X
    Keywords: Candida albicans ; hexetidine ; reduced adherence ; in vitro ; ex vivo ; modified morphogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study reports the effects of hexetidine (Oraldene™) on two virulence attributes of Candida albicans, namely,in vitro and ex vivoadherence of yeast cells to buccal epithelial cells (EEC) and in vitro morphogenesis. Methods. The effects of hexetidine treatment of either yeast cells (stationary and exponential phases) or BEC on Candidal adherence, in terms of viable and non-viable adherent yeast cells, were evaluated using an acridine orange stain in conjunction with fluorescence microscopy. Ex vivoanti-adherence effects were determined by rinsing BEC in vivo with hexetidine (0.1%), removal of BEC after defined periods and inclusion in the adherence assay. The effects of hexetidine on morphogenesis were evaluated using light microscopy. Yeast cell viability following exposure to a range of concentration of hexetidine (0.005-0.1 % v/v) for defined periods was determined following serial dilution and enumeration on solid media. Results. Treatment of stationary and exponential phase yeast cells or BEC with hexetidine (0.1%) for a range of times (10−300 s) or, alternatively, with a range of concentrations of hexetidine (0.005−0.1 %) for a fixed time (30s) significantly decreased the resultant Candidal/ epithelial adhesion. No correlations were observed between reduced adherence and either time of treatment or hexetidine concentration. In vivotreatment of BEC with hexetidine (0.1%) for 30s resulted in prolonged and significant reductions in the ex vivo adherence of both viable and non-viable yeast cells for periods of up to (and including) four hours post-rinsing. Treatment of C. albicans blastospores with hexetidine (0.05, 0.1% v/v) for 10s and 30s totally inhibited Candida morphogenesis, whereas treatment with lower antiseptic concentrations significantly reduced the extent of Candida morphogenesis and the rate of hyphal development. The effects of hexetidine on yeast cell viability were both concentration and time-dependent. Conclusions. The reduced adherence of C. albicans to BEC and the modification or inhibition of morphogenesis following exposure to hexetidine suggests a clinical role for hexetidine in the prophylaxis of both superficial candidosis and the systemic complications resulting from invasion of sub-epithelial tissue.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 14 (1997), S. 450-457 
    ISSN: 1573-904X
    Keywords: texture profile analysis ; bioadhesion ; semi-solids ; hardness ; compressibility ; adhesiveness ; cohesiveness ; flow rheometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine. Methods. Textural analysis was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in texture profile analysis (TPA) mode. In this, an analytical probe was twice compressed into each formulation to a defined depth (15 mm) and at defined rates (2, 4, 6, 8, 10 mm s−1), allowing a delay period (15 s) between the end of the first and beginning of the second compressions. Flow rheograms were performed using a Carri-Med CSL2-100 rheometer with parallel plate geometry under controlled shearing stresses at 20.0 ± 0.1°C. Results. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymer significantly increased formulation hardness, compressibility, adhesiveness and zero-rate viscosity. Increased hardness and compressibility were due to the attendent increased viscosities of these formulations. Increased adhesiveness was related to the concentrations of the (bioadhesive) polymers employed in these formulations and, in addition, was dependent on the physical state of polycarbophil. Formulation viscosity contributed to product adhesiveness, reflecting the importance of product rheology on this parameter. Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC and HEC (3−5%w/w) were increased, was due an increase in semi-solid character. Numerical values of hardness, compressibility and adhesiveness were affected by the choice of probe speed, a parameter related to rate of shear in flow rheometry. Statistical interactions were observed and were assigned to the effects of HEC on the physical state of PVP (dissolved or dispersed) and PC (swollen or unswollen). Conclusions. This study has demonstrated both the applicability of textural analysis for the mechanical characterisation of bioadhesive semi-solid gel systems and, additionally, the direct influence of viscosity on the parameters defined by textural analysis, namely, hardness, compressibility and adhesiveness.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-904X
    Keywords: bioadhesion ; viscoelastic ; oscillatory rheometry ; storage modulus ; loss modulus ; loss tangent ; dynamic viscosity ; oropharynx
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx. Methods. Oscillatory rheometry was performed using a Carri-Med CSL2-100 rheometer at 20.0 ± 0.1° C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 × 10−3 rad) and defined viscoelastic parameters, namely storage modulus (G′), loss modulus (G″), loss tangent (tan δ) and dynamic viscosity (η′), measured over a defined frequency range (0.01-1.0 Hz). Results. As the oscillatory frequency was increased, G′ G″ of all formulations increased, whereas both η′ and tan δ significantly decreased. The magnitude of increase of G′ and G″ as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G′, G″,η′ yet decreased tan δ′ observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan δ decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient 'free-water' was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation η′ increased due to the attendent effects of polymer chain entanglement and polymer state on overall formulation viscosity. Conclusions. Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 61 (1996), S. 2229-2234 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: This study reports the use of texture profile analysis (TPA) to mechanically characterize polymeric, pharmaceutical semisolids containing at least one bioadhesive polymer and to determine interactions between formulation components. The hardness, adhesiveness, force per unit time required for compression (compressibility), and elasticity of polymeric, pharmaceutical semisolids containing polycarbophil (1 or 5% w/w), polyvinylpyrrolidone (3 or 5% w/w), and hydroxyethylcellulose (3, 5, or 10% w/w) in phosphate buffer (pH 6.8) were determined using a texture analyzer in the TPA mode (compression depth 15 mm, compression rate 8 mm s-1, 15 s delay period). Increasing concentrations of polycarbophil, polyvinylpyrrolidone, and hydroxyethylcellulose significantly increased product hardness, adhesiveness, and compressibility but decreased product elasticity. Statistically, interactions between polymeric formulation components were observed within the experimental design and were probably due to relative differences in the physical states of polyvinylpyrrolidone and polycarbophil in the formulations, i.e., dispersed/dissolved and unswollen/swollen, respectively. Increased product hardness and compressibility were possibly due to the effects of hydroxyethylcellulose, polyvinylpyrrolidone, and polycarbophil on the viscosity of the formulations. Increased adhesiveness was related to the concentration and, more importantly, to the physical state of polycarbophil. Decreased product elasticity was due to the increased semisolid nature of the product. TPA is a rapid, straightforward analytical technique that may be applied to the mechanical characterization of polymeric, pharmaceutical semisolids. It provides a convenient means to rapidly identify physicochemical interactions between formulation components. © 1996 John Wiley & Sons, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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