Matrix modifications modulate ophthalmic drug delivery from photo-cross-linked poly(propylene fumarate)-based networks.

In this work, different modifications of photo-cross-linked poly(propylene fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM) was increased by adding various amounts of poly(ethylene glycol) (PEG) or by increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior to cross-linking. The in vitro release studies that utilized high-performance liquid chromatography for quantification revealed highly accelerated drug release from the matrices with increasing contents of the hydrophilic modifier. AZ was released from matrices containing 5% PEG in 56 days, which equals approximately 25% of the release period found for the unmodified matrices. A comparable acceleration in drug release was found for TM-loaded samples modified with 5% PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM release duration by one-third. A significant acceleration in drug release was also found for the samples that were fabricated from a PPF-NVP mixture with increased NVP content. Matrix water content and erosion were assessed gravimetrically. Micro-computed tomography was used to image structural changes of the release systems and shed light on the drug-release mechanism. This study showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the drug release of two ophthalmic drugs and represent a suitable tool to adjust drug-release rates from PPF-based matrices for different therapeutic needs.

Biodegradable fumarate-based drug-delivery systems for ophthalmic applications.

The function of a photocrosslinked poly(propylene fumarate) (PPF)/poly(N-vinyl pyrrolidone) (PVP) matrix for the sustained release of three ophthalmic model drugs, acetazolamide (AZ), dichlorphenamide (DP), and timolol maleate (TM), was investigated. The drugs differ in molecular weight and degree of dissociation in aqueous environments; both are parameters that significantly influence drug diffusivity. AZ, DP, and TM-loaded cylindrical rods (10 mm length, 0.6 mm diameter) were fabricated by photoinduced cross-copolymerization of PPF and N-vinyl pyrrolidone (NVP) in molds. The released amounts of AZ, DP, TM, and NVP were determined by high-performance liquid chromatography (HPLC). The effects of drug properties and loading on the release kinetics were investigated. The in vitro release of AZ, DP, and TM was well sustained from the polymer matrices over a period of approximately 210, 270, and 250 days, respectively. The release kinetics correlated with the HPLC retention profiles of the different drugs. Following a small initial burst release (<10%), a dual modality release controlled by diffusion and bulk erosion was found for all drugs. Drug release rates of up to 4 microg/day were reached. Matrix drug loading generally affected the extent of the burst release, release kinetics, as well as the matrix water content and matrix degradation that were determined gravimetrically. Microcomputed tomography was used to image structural and dimensional changes of the devices. A preliminary rabbit implantation study revealed promising ocular biocompatibility of drug-free PPF/PVP matrices. All results indicate the potential of photocrosslinked PPF-based matrices as polymeric carriers for long-term ophthalmic drug delivery.

Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.

This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery.

Long-term release of fluocinolone acetonide using biodegradable fumarate-based polymers.

Intraocular drug delivery systems made from biodegradable polymers hold great potential to effectively treat chronic diseases of the posterior segment of the eye. This study is based on the hypothesis that crosslinked poly(propylene fumarate) (PPF)-based matrices are suitable long-term delivery devices for the sustained release of the anti-inflammatory drug fluocinolone acetonide (FA) due to their hydrophobicity and network density. FA-loaded rods of 10 mm length and 0.6 mm diameter were fabricated by photo-crosslinking PPF with N-vinyl pyrrolidone (NVP). The released amounts of FA and NVP were determined by HPLC analysis. The effects of drug loading and the ratio of PPF to NVP on the release kinetics were investigated using a 2(3-1) factorial design. Overall, FA release was sustained in vitro over almost 400 days by all tested formulations. Low burst release was followed by a dual modality release controlled by diffusion and bulk erosion with release rates up to 1.7 microg/day. The extent of the burst effect and the release kinetics were controlled by the drug loading and the matrix composition. Matrix water content and degradation were determined gravimetrically. Micro-computed tomography was used to image structural and dimensional changes of the devices. The results show that photo-crosslinked PPF-based matrices are promising long-term delivery devices for intraocular drug delivery.

Efficacy of multipurpose solutions against Acanthamoeba species.

AIM: The disinfection efficacy of contact lens multipurpose solutions (MPSs) against Acanthamoeba polyphaga (Ros) and Acanthamoeba castellanii (ATCC30868) cysts and trophozoites was determined by both biocidal and manufacturer-recommended no-rub/rinse regimen testing. METHODS: A biocidal assay using four MPSs (ReNu with MoistureLoc, Opti-free Express, Solo-care Plus, and Complete MoisturePlus) was conducted with or without the presence of organic soil. A second test procedure compared the ability of five MPSs (ReNu with MoistureLoc MPS, ReNu MultiPlus, Opti-free Express, Solo-care Aqua, and Complete MoisturePlus) to remove and kill Acanthamoeba species cysts and trophozoites from SofLens 38 and Surevue conventional hydrogel lenses, and Focus Night & Day silicone hydrogel lenses using the manufacturer-recommended regimen. RESULTS: In the biocidal assay, only ReNu with MoistureLoc successfully killed both trophozoites and cysts (>3 log) within the manufacturer-recommended soak time. A >3 log decrease in trophozoites, but not cysts, was reported for Opti-free Express; however, Solo-care Plus and Complete MoisturePlus did not reduce the number of cysts or trophozoites by >3 log during the manufacturer-recommended soak time. In the no-rub/rinse regimen tests, only ReNu with MoistureLoc removed an inoculum of 2 x 10(5) trophozoites or cysts from SofLens 38 and Surevue hydrogel lenses, as well as Focus Night & Day silicone hydrogel lenses. Less than 10 viable organisms were recovered from the lenses after the 10s rinse and 4h soak. Opti-free Express, Solo-care Aqua, and ReNu MultiPlus were effective at removing trophozoites and cysts from SofLens 38 and Surevue conventional hydrogel lenses, but not from Focus Night & Day silicone hydrogel lenses. In excess of 10 viable organisms were recovered from all lenses after the manufacturer-recommended regimen using Complete MoisturePlus. CONCLUSIONS: These data suggest that some MPSs, when used as recommended by the manufacturer, are more effective at killing representative strains of Acanthamoeba than others.

Comparative antimicrobial efficacy of multi-purpose hydrogel lens care solutions.

Ten single-bottle multipurpose hydrogel lens care solutions commercially available in the European market were evaluated for antimicrobial efficacy using the International Organization for Standardization's (ISO) Stand-Alone Procedure. The results of this study indicate that ReNu Multi Plus ReNu Multi Purpose, Complete and DUA meet the ISO Stand-Alone primary acceptance criteria for stand-alone disinfectants against all challenge organisms: Staphylococcus aureus, Serratia marcescens, Pseudomonas aeruginosa, Candida albicans, and Fusarium solani. Solo-Care Soft, All-In-One Light, Optiplus, Opti Free Express, UniCare and Combi Comfort do not meet the ISO Stand-Alone primary acceptance criteria for one or more test organisms within their respective labelled minimum disinfection times. In addition, although not a requirement of the guidance document, only ReNu MultiPlus and ReNu Multi-Purpose exceeded the minimum ISO Stand Alone primary acceptance criteria within 25% (1 h) of their labelled minimum disinfection time for all test organisms. This evaluation provides a direct comparison of antimicrobial activity for commercially available multipurpose lens care solutions at their labelled minimum disinfection times. The results of this study should be considered when selecting appropriate lens care systems for patients.

Effects of hydrogel/silver coatings on in vitro adhesion to catheters of bacteria associated with urinary tract infections.

Sections of sterile all-silicone-, hydrogel/silver-all-silicone-, and hydrogel/silver-latex-Foley urinary catheters were exposed to suspensions of bacteria and Candida albicans associated with urinary tract infections. The adhesion of these microorganisms to the catheters was determined with a radiolabel-cell procedure and scanning electron microscopy. Anomalous data with the radiolabel procedure were produced with the hydrogel/silver-latex catheters for certain species. These aberrant data were related to adhesion on the untreated cut ends of the latex catheter. Radiolabel-cell-adhesion procedures that involve sections of coated materials may need to be supplemented with additional procedures such as scanning electron microscopy for valid interpretations of the data. Adhesion to the hydrogel/silver catheters by both Gram-positive- and Gram-negative bacteria most commonly associated with nosocomial urinary tract infections, including a strain of Pseudomonas aeruginosa noted for its superior adhesion capacity, was significantly lower than the adhesion to the control all-silicone catheter.

Flow cytometry for determination of the efficacy of contact lens disinfecting solutions against Acanthamoeba spp.

Flow cytometric analyses of cellular staining with fluorescent viability dyes and direct microscopic observations of methylene blue exclusion were compared for evaluation of the effects of a chlorhexidine gluconate-based contact lens disinfectant solution and a polyhexamethylene biguanide solution against cysts and trophozoites of Acanthamoeba castellanii and Acanthamoeba polyphaga. The flow cytometric procedure with propidium iodide (used to stain dead cells) indicated that more than 90% of trophozoites of both species (inocula of 10(5) to 10(6)/ml) at 22 degrees C lost their viability after 4 h of exposure to chlorhexidine. When propidium iodide was used in combination with fluorescein diacetate (for live cells), the apparent number of propidium iodide-stained cells was reduced, but the relative efficacies of the two biguanide solutions appeared unchanged from those evident with the single dyes; the chlorhexidine solution was more effective than the polyhexamethylene biguanide solution. Similar data were obtained with the more cumbersome methylene blue exclusion procedure. Flow cytometric analyses provided a statistically reproducible and rapid procedure for determining the relative antiamoebal efficacies of the disinfecting solutions.

Comparison of 5.8S and ITS2 rDNA RFLP patterns among isolates of Acremonium obclavatum, A. kiliense, and A. strictum from diverse sources.

Polymerase chain reaction (PCR) products of nuclear 5.8S and internal transcribed spacer regions (ITS2) of rDNA from reference cultures of Acremonium obclavatum (a rarely recognized species first reported from India) were compared with cultures of Acremonium spp. isolated from Georgia, USA. Digestion of amplicons sequentially with Hinfl and Sau3AI divided the isolates into four restriction fragment length polymorphism (RFLP) groups. A representative isolate of primary colonizers of insulation facings from a building in Georgia appeared identical to the type culture of A. obclavatum, whereas other cultures from Indian soils showed variation in the ITS2 region that divided them into further subgroups. Reference cultures of A. kiliense (ATCC 14489) and A. strictum (ATCC 10141) and two additional isolates from metropolitan Atlanta, assigned to this latter species complex on a morphological basis, represented two additional RFLP groups both of which were distinct from the RFLP groups in A. obclavatum. A. kiliense and A. strictum could be placed into similar subgroups on the basis of morphological differences and distinct RFLP patterns.