Enhancing the efficacy of fluocinolone acetonide by encapsulating with PLGA nanoparticles and conjugating with linear PEG polymer.

Fluocinolone acetonide (FA), a glucocorticoid is used to treat inflammation in the posterior segment of the eye. Due to short half-life and body clearance, it will not be able to give therapeutic effect for long time with a single injection. Formulating FA nanoparticles (NPs) or PEG conjugates can be an effective way to overcome these disadvantages. We prepared two formulations, FA loaded in PLGA nanoparticles (NPs-FA) and FA conjugated to linear PEG (PEG-FA). The NPs-FA were characterised for size and zeta potential using particle size analyser and shape and morphology by using scanning electron microscope (SEM). The amount of drug loaded per mg of NPs and in-vitro release of FA from NPs were calculated using reverse phase high pressure liquid chromatography (RP-HPLC). NPs synthesis was optimized with factorial and Response Surface Methodology (RSM). Chemically synthesized PEG-FA conjugates were characterized using H-NMR and purity of the conjugate was analysed using RP-HPLC. Visualization of cellular uptake of NPs was done by coumarin-6 loaded NPs under fluorescent microscope. RAW 264.7 macrophages were treated with NPs-FA and PEG-FA conjugates to study their effectiveness in inhibiting TNF-α levels compared to free FA treatment. Stability test confirmed that FA is more stable within NPs than in free form. Particle size and zeta potential were found to be 183.6 ± 12.47nm and -25.6 ± 4.4mV, respectively. 149.58 ± 11.3µg of FA was encapsulated per mg of NPs and 61 µg of FA was present per mg of PEG-FA conjugate. In vitro drug release study showed a sustained release of FA from the NPs for a period of 30 days. Fluorescent microscope images showed uptake of NPs by RAW 264.7 cells. TNF-α assay confirmed that substantial inhibition of TNF-α levels from both formulations compared to free FA. From the results, we conclude that new formulations will greatly reduce drug dosage and frequency of administration for long term treatment of inflammation in posterior part of the eye.

In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products.

PURPOSE: To establish an in vivo-relevant Transwell dish-based dissolution test system for the "respirable" aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products. METHODS: "Respirable" ≤ 5.8 or 6.5 µm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell's supporting membrane. RESULTS: While three ICSs with high-to-intermediate solubility enabled the first-order "sink" and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order "non-sink", slow and limited dissolution. The aerosol dissolution rate constants (kdiss) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection. CONCLUSIONS: The in vivo-relevant Transwell dish-based "respirable" aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.

Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import.

Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti-IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential.

Development of Nanofibrous Ocular Insert for Retinal Delivery of Fluocinolone Acetonide.

PURPOSE: Topical formulations are less effective in treating retinal inflammatory diseases due to poor avaliability of drug at target tissues. Nanofibers due to their unique structural features show great promise for drug delivery to retinal segment following topical application. AIM: The aim of the present study was to design preservative free controlled release ocular drug delivery system for improved drug availability at the target site with higher patient compliance. MATERIALS AND METHODS: The fluocinolone acetonide-loaded PCL nanofibers were prepared by electrospinning technique. Optimized formulation was chosen on the basis of outcome of inclusive in-vitro characterization, SEM, FTIR, XRD, in-vitro release, isotonicity, sterility, and biodegradibility. The relative efficacy of optimized formulation was investigated in rabbits against its marketed counter part. RESULTS: The prepared fibers were sterile, smooth, non-woven and they showed extended drug release behavior. Ocular and plasma kinetics showed therapeutic levels at the target site while minimizing systemic distribution. CONCLUSIONS: Preclinical results established that PCL nanofibers serve as a promising drug carrier for retinal segment.

Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray.

The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) (Y1) and D50 droplet size distribution (DSD) (µm) (Y2) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett-Burman and Box-Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) (Y1) was significantly impacted by formulation variables X1: propylene glycol (PG) (%) and X2: polyethylene glycol (PEG) 3350 (%), while D50 DSD (µm) (Y2) was significantly impacted by formulation variables X1: PG (%), X2: PEG 3350 (%) and device variable X8: delivery volume (µl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.

Fluocinolone Acetonide Intravitreal Implant 0.19 mg (ILUVIEN®): A Review in Diabetic Macular Edema.

Fluocinolone acetonide intravitreal implant 0.19 mg (ILUVIEN®) is a nonbiodegradable, injectable, corticosteroid implant that is approved in several countries, including the USA, for the treatment of diabetic macular edema (DME). ILUVIEN® releases fluocinolone acetonide at an initial rate of 0.25 µg/day (average rate 0.2 µg/day) and lasts 36 months. In the two pooled pivotal FAME trials in patients with DME previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0.2 µg/day was significantly more effective than sham injection with respect to the proportion of patients with an improvement from baseline in best-corrected visual acuity of ≥15 letters at 24 months (primary endpoint). This therapeutic effect was maintained at 36 months. The implant also significantly decreased foveal thickness at 24 months. FAME study results are broadly supported by real-world studies in patients with chronic DME considered insufficiently responsive to available therapies. Consistent with corticosteroid class-specific adverse events, cataract and elevated intraocular pressure (IOP) were the most common adverse events with the fluocinolone acetonide intravitreal implant. Raised IOP was treated with medications in most patients, with <5% requiring incisional IOP-lowering surgery. In the USA, fluocinolone acetonide intravitreal implant should be used only in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant increase in IOP. Available data indicate that fluocinolone acetonide intravitreal implant 0.19 mg is a useful option for the treatment of DME in these patients.

A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations.

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 µm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.

Design, characterization and skin permeating potential of Fluocinolone acetonide loaded nanostructured lipid carriers for topical treatment of psoriasis.

The aim of the current study was to develop and optimize Fluocinolone acetonide (FA) loaded nanostructured lipid carriers (NLC) and to evaluate its potential as topical delivery system for management of psoriasis. FA loaded NLCs were successfully developed by modified microemulsion method and optimized using 3-level Box-Behnken design. NLCs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment efficiency and drug loading. Further X-ray diffraction (XRD) and Differential scanning calorimetry (DSC), in vitro release, in vitro skin distribution and stability study were also performed. Transmission electron microscopy confirmed spherical shape of prepared NLCs. Complete encapsulation of drug in the nanoparticles was confirmed by XRD and DSC. Release study showed prolonged drug release from the NLCs following Higuchi release kinetics and Zero order release kinetics, whereas pure FA suspension exhibited faster drug release following Zero order release kinetics with R(2) value of 0.995. Stability study confirmed that NLCs were stable for 3months at 4°C. Furthermore, in vitro skin distribution studies showed presence of significant amount of FA in the epidermal and dermal layer of skin when treated with FA loaded NLCs suspension while plain FA suspension showed significantly lesser amount of FA in the epidermis and dermis. Moreover, selective retention of FA in the epidermis might eliminate adverse side effects associated with systemic exposure. Thus FA loaded NLCs could be a potential system for psoriasis treatment but to create clinical value of the present system further studies are needed in clinically relevant models.

The Effect of Active Pharmaceutical Ingredients on Aerosol Electrostatic Charges from Pressurized Metered Dose Inhalers.

PURPOSE: This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators. METHODS: Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.3 mm nominal orifice diameter and cone nozzle shape. Aerosol electrostatics for each pMDI formulation and actuator were evaluated using the electrical low-pressure impactor (ELPI) and drug depositions were analysed using high performance liquid chromatography (HPLC). RESULTS: All three actuator materials showed the same net charge trend across the five active drug ingredients, with BDP, BUD and FS showing positive net charges for both nylon and PTFE actuators, respectively. While SB and IPBr had significantly negative net charges across the three different actuators, which correlates to the ionic functional groups present on the drug molecule structures. CONCLUSIONS: The API present in a pMDI has a dominant effect on the electrostatic properties of the formulation, overcoming the charge effect arising from the actuator materials. Results have shown that the electrostatic charges for a solution-based pMDI could be related to the interactions of the chemical ingredients and change in the work function for the overall formulation.

Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-ß3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration.

Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-ß3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-ß3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-ß3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-ß3-associated chondrogenesis, and suggest that the FA/TGF-ß3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-ß3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells.

Fluocinolone acetonide intravitreal implant (Iluvien®): in diabetic macular oedema.

Fluocinolone acetonide intravitreal implant (Iluvien®) is an injectable, non-erodible, corticosteroid implant that is approved in several European countries for the treatment of chronic diabetic macular oedema (DMO). In analyses of two multinational trials in patients with DMO previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0.2 µg/day was significantly more efficacious than sham injection in improving visual acuity. At 24 months post injection, 29 % of fluocinolone acetonide intravitreal implant 0.2 µg/day recipients had an improvement in the best-corrected visual acuity (BCVA) letter score of ≥15 compared with 16 % in the sham injection group (p = 0.002) [primary endpoint]. Treatment benefit was most evident in the subgroup of patients whose duration of DMO was ≥3 years. In this subgroup at 36 months, 34 % of fluocinolone acetonide intravitreal implant 0.2 µg/day recipients had an increase in the BCVA score of ≥15, compared with 13 % of sham injection recipients (p < 0.001). Fluocinolone acetonide intravitreal implant recipients also had generally greater benefits than sham injection recipients on secondary endpoints. In patients who were phakic in the study eye at baseline, cataracts occurred in 82 % of fluocinolone acetonide intravitreal implant 0.2 µg/day recipients and 51 % of sham injection recipients. Overall, 37 % and 12 % of patients in the fluocinolone acetonide intravitreal implant and sham injection groups developed raised intraocular pressure (IOP), which was generally controlled with IOP-lowering drugs.

Incorporation of anti-inflammatory agent into calcium hydroxide pulp capping material: an in vitro study of physical and mechanical properties.

The aims of this study were to investigate the release of fluocinolone acetonide from an experimental pulp capping material containing fluocinolone acetonide (PCFA) and compare some physical and mechanical properties with Dycal(®). The PCFA is a hard-setting calcium hydroxide cement composed of 50 mmol/L fluocinolone acetonide. Conditioned media from the setting material was collected for determination of fluocinolone acetonide release by high performance liquid chromatography and pH measurement by pH meter. The setting time, compressive strength, disintegration, and acid soluble arsenic content were measured according to ISO 3107:2004. Dycal(®) was used as control. Fluocinolone acetonide could release at a range of suitable concentrations from PCFA. The pH, setting time, and acid soluble arsenic content of PCFA were significantly higher than those of Dycal(®). The compressive strength and disintegration of PCFA were comparable to control. PCFA may be considered as an alternative in pulp capping of inflamed dental pulp tissue.

Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 µg of FA conjugated to 7 µg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation.

Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts.

OBJECTIVE: To determine whether adverse effects such as elevated intraocular pressure and cataracts, which are lower with dexamethasone when compared with fluocinolone acetonide or triamcinolone acetonide, may be explained in part by the differences in drug lipophilicity and partitioning of these drugs into the trabecular meshwork and lens. METHODS: The n-octanol/phosphate-buffered saline (pH 7.4) partition coefficient (log distribution coefficient [D]) and bovine/human ocular tissue partition coefficients were determined for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide at 37°C. RESULTS: The log D of the corticosteroids ranged from 0.712 to 2.970. The ranges of tissue:PBS partition coefficients following drug incubation at 0.4, 2.0, and 10.0 µg/mL were 0.35 to 1.56, 0.30 to 2.12, and 0.30 to 1.95, respectively, for the bovine lens, 0.87 to 4.18, 0.71 to 4.40, and 0.69 to 5.86, respectively, for the human lens, and 2.98 to 9.48, 2.41 to 9.16, and 1.71 to 9.96, respectively, for the bovine trabecular meshwork. In general, tissue partitioning showed a positive correlation with log D. Dexamethasone, with lipophilicity less than triamcinolone acetonide and fluocinolone acetonide, exhibited the least amount of partitioning in the trabecular meshwork and lens among these 3 corticosteroids commonly used for treating diseases at the back of the eye. CONCLUSION: Binding of corticosteroids to the trabecular meshwork and lens increases as drug lipophilicity increases. CLINICAL RELEVANCE: Less lipophilic corticosteroids with limited partitioning to the trabecular meshwork and lens may result in reduced incidence of elevated intraocular pressure and cataracts.

Investigation of solvolysis kinetics of new synthesized fluocinolone acetonide C-21 esters--an in vitro model for prodrug activation.

In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO3. The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 °C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.

Photoactivation of corticosteroids in UVB-exposed skin.

The photodegradation of flumethasone (FM) and fluocinolone acetonide (FC) was studied in solution and in the pig skin. Both glucocorticosteroids applied to the pig skin were unstable under UVB light. The photoproducts formed in the skin were the lumi-, photolumi- and andro-derivatives for FM, the same found in vitro. Instead, FC hydroperoxide formed in solution was not found in the skin: the reactivity and oxidative ability of this photoproduct towards biological substrates (lipids, proteins) seems the reason of the lack of its detection in the ex vivo model. In fact, it demonstrated to quickly oxidize amino acids and peptides, and to react with BSA both in the dark and under irradiation. Moreover, the presence in the irradiated pig skin of the FC andro-derivative, which usually forms in H-donating environment, seems consistent with the mechanism of Norrish I fragmentation followed by H-abstraction, likely from the surrounding biological substrates. These findings indicate that photoreactivity of these compounds may take place in the skin of patients exposing themselves to sunlight and is a warning about possible skin damage as a result of that. Furthermore, photolability of these drugs in the skin might cause loss of their therapeutic activity.

An application of second-order UV-derivative spectrophotometry for study of solvolysis of a novel fluocinolone acetonide ester.

A novel topical corticosteroid FA-21-PhP, 2-phenoxypropionate ester of fluocinolone acetonide, has been synthesized in order to investigate the possibility of decreasing systemic side effects. In this study model system for in vitro solvolytic reaction of FA-21-PhP has been analyzed in ethanol/water (90:10, v/v) with excess of sodium hydrogen carbonate. The selected conditions have been used as in vitro model for activation of corticosteroid C-21 ester prodrug. The second-order derivative spectrophotometric method (DS) using zero-crossing technique was developed for monitoring ternary mixture of solvolysis. Fluocinolone acetonide (FA) as a solvolyte was determined in the mixture in the concentration range 0.062-0.312 mM using amplitude (2)D(274.96). Experimentally determined LOD value was 0.0295 mM. The accuracy of proposed DS method was confirmed with HPLC referent method. Peak area of parent ester FA-21-PhP was used for solvolysis monitoring to ensure the initial stage of changes. Linear relationship in HPLC assay for parent ester was obtained in the concentration range 0.054-0.54 mM, with experimentally determined LOD value of 0.0041 mM. Investigated solvolytic reaction in the presence of excess of NaHCO(3) proceeded via a pseudo-first-order kinetic with significant correlation coefficients 0.9891 and 0.9997 for DS and HPLC, respectively. The values of solvolysis rate constant calculated according to DS and HPLC methods are in good accordance 0.038 and 0.043 h(-1), respectively.

Compressor/nebulizers differences in the nebulization of corticosteroids. The CODE study (Corticosteroids and Devices Efficiency).

BACKGROUND: Nebulization is a common method of medical aerosol generation and it is largely used by adults and children all over the world, both for emergency treatment of acute illness and for long-term home treatment of lung diseases. The aim of this study was to determine the differences in nebulization of inhaled corticosteroids among four representative types of compressor/nebulizers. METHODS: Twelve compressor/jet nebulizers from four commercial sources were studied (three for each type): Clenny (MEDEL), Turbo Boy/LC Plus (PARI), Nebula Nuovo/MB5 (MARKOS MEFAR) and Maxaer (ARTSANA) compressor/Sidestream (Medic-Aid Ltd.) nebulizer. We compared the required time for the treatment (nebulization time), output/minutes, compressor pressures, and aerosol characteristics of inhaled corticosteroids: Beclomethasone dipropionate, Flunisolide, Fluticasone propionate and Budesonide. RESULTS: Nebulization Times showed a significant difference between nebulizer and inhaled corticosteroids for Clenny, Turbo Boy, and Maxaer. A considerable difference in the output of nebulized drugs was observed through the compressors/nebulizers. MMAD of all inhaled corticosteroids was significantly different among the four nebulizers. The percentage of particles <5 microm (respirable range) was high for all devices with beclomethasone and budesonide (> 90%), whereas with flunisolide was good only for Clenny (98.8%) and Maxaer (96.3%), and with fluticasone only for Clenny (98%), Turbo Boy (99.1%), and Maxaer (86%). Also percentage of particles <2 microm showed significant variability among the devices. CONCLUSIONS: Our results clearly demonstrate that compressor/nebulizer unit plays a key role in the effectiveness of the treatment during inhaled corticosteroid therapy, and that several differences exist in the performance of the different nebulizers studied. Therefore, the device has the same importance of the compound to reach the best clinical response in the inflammatory diseases of the lower airways.

Fluocinolone acetonide intravitreal sustained release device--a new addition to the armamentarium of uveitic management.

Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale.