Betamethasone Sodium Phosphate Research Articles

Photocatalytic degradation of betamethasone sodium phosphate in aqueous solution using ZnO nanopowder

The photocatalytic degradation of betamethasone sodium phosphate has been investigated in aqueous phase by using ultraviolet (UV) light and ZnO nanopowder. The effect of catalyst loading, irradiation time, pH, addition of oxidizers, effect of alcohol and anion presence on the reaction rate was ascertained and optimum conditions for maximum degradation were determined. The photocatalytic degradation of betamethasone sodium phosphate was strongly influenced by these parameters. The optimum amount of the photocatalyst used is 0.44 g/L. The efficiency of betamethasone sodium phosphate increases with the photo-degradation increase of the irradiation time.

Determination of the Particulate Size and Aggregation of Clonidine and Corticosteroids for Epidural Steroid Injection

Background: Epidural injection of corticosteroids is a commonly used treatment for radicular pain. However, the benefits are often short lived, and repeated injections are often limited secondary to concerns of side effects from cumulative steroid doses. In addition, rare, catastrophic complications, including brain and spinal cord embolic infarcts have been attributed to particulate steroid injections. A previous study has shown that dexamethasone has less particulate than other corticosteroids, possibly reducing embolic risk. Furthermore, a recent study indicated that clonidine may be useful in the treatment of radicular pain when administered via epidural steroid injection. The combination of corticosteroid and clonidine is an intriguing, yet unstudied, alternative to traditional treatment. Objective: Our study examines whether mixing clonidine and various corticosteroids results in increased particle size or aggregation. Methods: Evaluations under light microscopy for particle size were made of samples of clonidine alone and clonidine mixed with equal parts of 3 corticosteroids solutions: dexamethasone sodium phosphate injection, triamcinolone acetonide injectable suspension, and betamethasone sodium phosphate and betamethasone acetate injectable suspension. Four mL each of clonidine (100 μcg/ mL), clonidine (100 μcg/mL) + dexamethasone sodium phosphate injection (4 mg/mL), clonidine (100 μcg/mL) + triamcinolone acetonide injectable suspension (40 mg/mL), and clonidine (100 μcg/mL) + betamethasone sodium phosphate and betamethasone acetate injectable suspension (6 mg/mL) were examined Their particle sizes were compared to measurements taken when each steroid solution was examined alone. Results: Clonidine was determined to be nonparticulate when examined by light microscopy. Clonidine mixed with equal parts of each of the 3 corticosteroids mentioned above did not result in increased clumping or increased particle size over each of the corticosteroids measured alone. Conclusion: Mixing clonidine with corticosteroids did not increase particulation compared to corticosteroids alone. Combining clonidine and corticosteroids for epidural injection may prove to be a useful treatment for radicular pain. The combination of these is unlikely to result in a solution that is more likely to cause embolic infarcts than the use of corticosteroids alone. Key words: steroid, epidural, clonidine, injection, particulate, aggregation

Desenvolvimento e validação de método analítico por CLAE para a quantificação simultânea de dipropionato de betametasona e fosfato sódico de betametasona em suspensão injetável

A reversed-phase HPLC method was developed and validated to separate and simultaneously quantify the association of betamethasone sodium phosphate (BP) and betamethasone dipropionate (BD) in injectable suspensions. Chromatographic conditions were ternary gradient elution at 1.6 mL/min on a C18 column with 254 nm. The linearity of the method was established in the range 120 to 280 mg/mL BD, and 48 to 112 mg/mL BP. The RSD of intermediate precision of the method was <1% and recoveries were 99-101% for both drugs. The method proved selective, linear, precise, accurate and robust for quantifying BP and BD in commercial injectable suspensions.

Spectral domain optical coherence tomography study of pearl-like lesions in the anterior chamber

AimTo study the morphological pattern of pearl-like lesions in the anterior chambers of children before and after management using anterior segment spectral domain optical coherence tomography (SD-OCT).Patients and methodsThis was a prospective, observational cross-sectional study of patients presenting with peculiar pearl-like lesions in the anterior chamber of their eyes. 1 mL of betamethasone sodium phosphate (2 mg/mL) and betamethasone dipropionate (5 mg/mL) was injected subconjunctivally. Follow-ups of all patients were conducted for a period of 6 weeks. Anterior segment imaging was done using SD-OCT and also photo slit lamp before and after management.ResultsTwelve eyes of 12 patients were included in this study. These patients presented with pearl-like lesions in the anterior chamber with signs of anterior uveitis. There was no history of ocular injury or tuberculosis in any patients. Six weeks after subconjunctival steroid injection, all patients achieved mean best-corrected visual acuity, which changed from 0.2 (range 0.1–0.4) to 0.5 (range 0.4–0.8), and the severity of iritis decreased. SD-OCT showed that the lesions at presentation appeared as a globular noncystic mass attached to the back of the cornea, encroaching on the angle of the eye, and attached to the anterior surface of the iris at some points.ConclusionSD-OCT for imaging the anterior segment allowed us to exclude the cystic nature of this pearly lesion. Some similarities may exist between these pearly lesions and superficial phlyctenular keratitis, which may support the immunological and inflammatory origin of these lesions.

The chondrotoxicity of single-dose corticosteroids

Corticosteroids are commonly injected into the joint space. However, studies have not examined the chondrotoxicity of one-time injection doses. The purpose of this study is to evaluate the effect of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), and triamcinolone acetonide (Kenalog) on human chondrocyte viability in vitro. Single-injection doses of each of the corticosteroids were separately delivered to human chondrocytes for their respective average duration of action and compared to controls using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A 14-day time-controlled trial was also performed. A live/dead reduced biohazard viability/cytotoxicity assay was used to quantify chondrocyte viability. Over their average duration of action, betamethasone sodium phosphate/acetate solution and triamcinolone acetonide caused significant decreases in chondrocyte viability compared to control media (19.8 ± 2.9% vs. 5.2 ± 2.1%, P = 0.0025 and 10.2 ± 1.3% vs. 4.8 ± 0.9%, P = 0.0049, respectively). In the 14-day trial, only betamethasone sodium phosphate/acetate solution caused a significant decrease in chondrocyte viability compared to control media (21.5% vs. 4.6%, P < 0.001). A single-injection dose of betamethasone sodium phosphate and betamethasone acetate solution illustrated consistent and significant chondrotoxicity using a physiologically relevant in vitro model and should be used with caution. Given the observed chondrotoxicity of triamcinolone acetonide in a single trial, there may be some evidence that this medication is chondrotoxic. However, at 14 days, betamethasone sodium phosphate and betamethasone acetate was the only condition that caused significant cell death.

Pharmacokinetics of Betamethasone After Single-Dose Intramuscular Administration of Betamethasone Phosphate and Betamethasone Acetate to Healthy Subjects

BackgroundBetamethasone is used for its antiinflammatory and immunosuppressive effects in disorders of many organ systems. However, the pharmacokinetic properties of betamethasone in plasma after intramuscular injection of betamethasone sodium phosphate and betamethasone acetate dual-acting suspension need further investigation. ObjectivesThe main aim of this study was to determine the pharmacokinetic parameters of betamethasone, betamethasone acetate, and betamethasone phosphate after the administration of a single intramuscular dose of the dual-acting suspension to healthy human volunteers. MethodsTwo different studies were conducted in healthy males. Volunteers were judged healthy based on their medical history, physical examination, and laboratory test results. Before confinement, all volunteers were tested for freedom from alcohol and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg of betamethasone acetate was administered by intramuscular injection. Blood sampling covered 48 hours. The plasma samples obtained in the second study were stabilized to enable pharmacokinetic profiling of betamethasone esters. ResultsTwenty-four healthy males with mean (SD) age of 27 (6.62) years participated in each study. No incidences of serious adverse events were recorded during the studies. Six mild adverse events were reported in 2 subjects in the second study. One subject suffered from pain at the injection site and insomnia, and another subject complained of heartburn and drowsiness. Betamethasone phosphate appeared to be readily absorbed with a mean AUC0–t of 96.01 ng/h/mL and an AUC0–∞ of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration reached a mean t½ of 12.92 hours. Betamethasone acetate was not detected in the volunteers' plasma in either study (total of 2208 plasma samples). ConclusionThe observed pharmacokinetic parameters suggested that the acetate ester, and not the phosphate ester, of betamethasone acts as a prodrug or reservoir for betamethasone, conferring on it sustained- and extended-release characteristics.

Pharmacokinetics of betamethasone and betamethasone 17-monopropionate in Chinese healthy volunteers after intramuscular injection of betamethasone phosphate/betamethasone dipropionate

The aim of this study was to evaluate the pharmacokinetic profiles of betamethasone (BOH, CAS 378-44-9) and betamethasone 17-monopropionate (B17P), the active metabolites of betamethasone phosphate (BSP) and betamethasone dipropionate (BDP), respectively, after administration of betamethasone i.m. (BSP 2 mg and BDP 5 mg). After ten healthy volunteers had received a single-dose intramuscular adminitration of betamethasone i.m., blood samples were collected pre-dose and for 336 h postdose. The plasma levels of B17P and BOH were measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). When compared to BOH, B17P exhibited a longer time to maximum concentration (15.0 +/- 9.0 h vs. 2.8 +/- 1.7 h), a lower Cmax (0.6 +/- 0.2 ng/mL vs. 14.5 +/- 3.7 ng/mL), and a much longer half-life (80.8 +/- 22.7 h vs. 9.6 +/- 3.6 h). Betamethasone i.m. produced rapid onset and sustained action through an initial rapid-increased plasma concentration of BOH and a sustained plasma concentration of B17P, respectively.

Severe hiccups associated with intra-articular corticosteroid injection — A case report

Abstract A hiccup is a sudden contraction of the inspiratory and diaphragmatic muscles followed by an abrupt closure of the glottis; that produces a characteristic noise resulting from vibrations of the vocal cords. Brief episodes of hiccups are common in humans at all stages of life and are usually benign. Prolonged attacks that last for days or weeks are considered a more serious phenomenon and may indicate an underlying disorder warranting a comprehensive medical evaluation. These attacks have been associated with significant burden and morbidity. The most common triggers for acute hiccups are linked with gastro-intestinal causes, such as the gastric distension that occurs after an abundant meal, or with gastroesophageal disease. Sudden changes in temperature, excessive alcohol consumption, as well as excitement or emotional stress, may also set off acute hiccups. Certain drugs, including benzodiazepines, barbiturates, and many others, have been reported to induce hiccups. Drug-induced hiccups are diagnosed by exclusion of other causes and represent a very unusual side-effect of drugs like corticosteroids. We present a case of hiccups associated with intra-articular Diprospan (Betamethasone Sodium Phosphate) administration.

The effect of local anesthetic and corticosteroid combinations on chondrocyte viability

Local anesthetic and corticosteroid combination injections are often used in clinical practice, however research investigating the chondrotoxic properties of these combinations is minimal. The goal of this study was to evaluate the effect of single injection doses of 1% lidocaine or 0.25% bupivacaine in combination with single injection doses of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), or triamcinolone acetonide (Kenalog) on human chondrocyte viability. All treatment conditions were delivered to human chondrocytes in vitro for the medication's respective average duration of action using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A two-color fluorescence assay was used to evaluate cell viability. A mixed-effects regression model was used to evaluate the mean differences in cell viability between treatment groups. At 14 days, a single injection dose of 1% lidocaine or 0.25% bupivacaine in combination with betamethasone sodium phosphate and betamethasone acetate solution illustrated significant chondrotoxicity when compared with the local anesthetics alone (P < 0.01). Methylprednisolone acetate and Triamcinolone acetonide both showed significant evidence of chondrotoxicity (P = 0.013; P = 0.016, respectively) when used in combination with 1% lidocaine compared with lidocaine alone, but showed no significant chondrotoxicity in combination with 0.25% bupivacaine (P's = n.s.). Clinicians should use caution when injecting 1% lidocaine or 0.25% bupivacaine in conjunction with betamethasone sodium phosphate and betamethasone acetate solution due to its pronounced chondrotoxic effect in this study. 1% lidocaine used in combination with methylprednisolone acetate or triamcinolone acetonide also led to significant chondrotoxicity.

Paper # 155: Chondrotoxicity of Single Dose Corticosteroid Injections

A single injection dose of Betamethasone sodium phosphate and Betamethasone acetate solution illustrated significant chondrotoxicity using a physiologically relevant in-vitro model, which may be due to the preservative benzalkonium chloride or due to Betamethasone's crystalline structure, which is very similar to the monosodium urate crystals found in gout.

An LC-MS/MS-ESI method for the quantification of betamethasone in bioequivalence studies

Summary A simple, sensitive, and rapid liquid chromatography-mass detection (LC-MS/MS) method for the analysis of betamethasone (BET) from intramuscular injection of phosphate and dipropionate BET produgs was developed for bioequivalence studies in human plasma. The calibration curve was linear over the range of concentrations (0.5–50.0 ng mL−1; r2 = 0.99), showing a very high sensitivity without interferences at the retention times of BET (0.8 min) and the internal standard (IS) triamcinolone acetonide (0.95 min). Both drug (D) and IS were extracted from human plasma by liquid-liquid extraction, showing average recovery values of 94.0 and 98.9%, respectively. Within- and between-run precision studies demonstrated a variation coefficient <10% at all tested concentrations. Therefore, our analytical method proved to be validated according to the worldwide-accepted FDA guidelines and successfully applied for bioequivalence studies of parenteral formulations containing BET dipropionate (5 mg mL−1) and BET sodium phosphate (2 mg mL−1).

Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients receiving high-dose cytarabine and total body irradiation as a conditioning for hematopoietic stem cell transplantation

We previously reported a high incidence of kerato-conjunctivitis in patients receiving high-dose cytarabine following total body irradiation (TBI) as a conditioning for hematopoietic stem cell transplantation (HSCT) even on prophylaxis with topical corticosteroid. This study aimed to evaluate whether addition of eye rinse, which was designed to remove cytarabine from ocular surface, further reduces the incidence of kerato-conjunctivitis in the same setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m(2) every 12 h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated. All patients received betamethasone sodium phosphate eye drops. Twenty-three patients were further instructed to rinse their eyes with sterile saline every 10-15 min during and for two additional hours after the completion of each cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato-conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively. These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)] observed in 53 patients without eye rinse (P < 0.001 and P < 0.00001, respectively). These results strongly suggest that eye rinse effectively reduces the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI.

LC–MS/MS determination of betamethasone and its phosphate and acetate esters in human plasma after sample stabilization

Two specific liquid chromatography–mass spectrometric (LC–MS/MS) assays were developed and validated for the determination of betamethasone (BET), and its acetate (BA) and phosphate (BP) esters. The plasma and the blood used for the development and validation of these two methods were previously stabilized. Liquid–liquid extraction techniques were used after the addition of prednisolone as internal standard (IS). Samples were chromatographed using C8 column, while mass detection was carried out by electrospray ionization in the positive mode (ESI+). The method was proved linear over a working range 0.50–50.00 ng/ml for BET ( r 2 > 0.99), while BA linear range was 1.0–20.0 ng/ml ( r 2 > 0.99). Sensitivity was determined as 0.50 ng/ml for BET and 1.00 ng/ml for BA. Betamethasone phosphate LC–MS/MS method involved solid phase extraction after the addition of prednisolone phosphate as (IS). Separation was carried out using C18 column, while detection was by ESI+. The method showed good linearity over the working range 2.0–200.0 ng/ml ( r 2 > 099). Both methods were applied to determine BET, BA and BP in plasma samples obtained for pharmacokinetics studies in human.

Beneficial Pharmacological Effects of Selective Glucocorticoid Receptor Agonist in External Eye Diseases

Glucocorticoids exert their actions via the glucocorticoid receptor through at least 2 intracellular mechanisms, known as transrepression and transactivation. It has been hypothesized that transrepression is the basis of their anti-inflammatory effects, whereas transactivation has been assumed to cause their side effects. ZK209614, a recently identified, novel selective glucocorticoid receptor agonist, exerts strong transrepression and weak transactivation. The objective of this study was to determine whether its pharmacological effects can be dissociated from its side effects. For this, we employed in vitro assays and topical in vivo models. ZK209614 and dexamethasone were used in in vitro transrepression and transactivation assays. To evaluate anti-inflammatory and antiallergic activities in vivo, ZK209614 and betamethasone phosphate were tested in the carrageenan-induced conjunctivitis model and allergic conjunctivitis model in rats. To evaluate side effects in vivo, treatments with ZK209614 and betamethasone phosphate were tested for the ocular hypertensive effects in a feline model, each drug being administered topically. ZK209614 showed strong transrepression and weak transactivation in the in vitro assays. When given as eyedrops, ZK209614 and betamethasone phosphate each had an inhibitory effect on edema weight in the rat carrageenan-induced conjunctivitis model. In the rat allergic conjunctivitis model, ZK209614 reduced the elevated vascular permeability at a concentration of 0.1%. In the feline intraocular pressure (IOP)-elevation experiment, topically administered betamethasone phosphate elevated IOP, but ZK209614 had no effect on IOP. The present investigations suggest that ZK209614 eyedrops have both anti-inflammatory and antiallergic effects, but no unwanted IOP-elevating effect. On that basis, ZK209614 might be a promising candidate as an ophthalmic drug with a better therapeutic index than classic glucocorticoids.

Local steroid injection for management of different types of acute idiopathic orbital inflammation: an 8-year study

Purpose To evaluate the long-term efficacy of local injection of steroid in treatment of acute idiopathic dacryoadenitis, myositis, and diffuse anterior orbital inflammation. Methods This prospective noncomparative interventional case study included 47 patients with acute idiopathic orbital inflammation. The disease was acute idiopathic 1) dacryoadenitis in 31 patients, 2) myositis in 12 patients, and 3) anterior diffuse orbital inflammation in 4 patients. Betamethasone suspension of 2 to 4 ml (1 ml contains 2 mg betamethasone sodium phosphate and 5 mg betamethasone dipropionate) was injected inside the inflamed gland, around the inflamed muscle and periocular in the diffuse form. Postinjection cold compression was applied for 6 hours, and systemic nonsteroidal anti-inflammatory drugs were given for 2 weeks. Results Dramatic response was achieved within 7 days after injection in all cases. During the follow-up period up to 8 years, 2 patients (1 with myositis and 1 with diffuse orbital inflammation) had recurrence, which was improved by the second injection. Conclusions The excellent long-term results achieved will shift the treatment of idiopathic orbital inflammation from oral steroid therapy with its hazards to a safer local injection therapy.

A change in treatment from etanercept to infliximab was effective to control scleritis in a patient with rheumatoid arthritis

Editor, We experienced a case of scleritis that was difficult to control in a patient with rheumatoid arthritis (RA) under etanercept treatment. We changed the anti-TNF treatment from etanercept to infliximab and succeeded in controlling both RA and scleritis. A 66-year-old Japanese woman with RA of 8 years of duration took etanercept therapy (25 mg twice weekly) in combination with 5 mg oral prednisolone treatment for 8 months. She discontinued etanercept therapy for 4 weeks before the cataract surgery and restarted etanercept therapy after surgery. She developed scleritis 1 month after restarting etanercept treatment. She was being treated with topical eye drops (levofloxacin hydrate 0.5%, betamethasone sodium phosphate 1% and diclofenac sodium 0.1%). Three months after restarting etanercept retreatment, her scleritis was exacerbated. Her prednisolone was increased up to 30 mg with some reduction in scleritis, but it was not limited. Two months after increasing the prednisolone dosage, etanercept therapy was interrupted by her orthopaedist for 1 month because prednisolone therapy (30 mg) was enough to control RA without etanercept. The scleritis was completely limited 1 month after interruption in etanercept therapy. To taper the amount of prednisolone, etanercept treatment was started again. Prednisolone (30 mg) was tapered (10 mg biweekly up to 10 mg) 2 weeks after the second restart of etanercept treatment. The scleritis recurred 1 month after the second restart of etanercept. Prednisolone therapy was increased again up to 30 mg for 2 months to inhibit scleritis. According to the clinical course described above, etanercept therapy coincided with the timing of the flare-up of scleritis two times, and therefore, etanercept was suspected to cause the scleritis or was ineffective in reducing scleritis. We decided to change the anti-TNF drug from etanercept to infliximab to taper the amount of the prednisolone. Two months after beginning infliximab and methotrexate treatment, we succeeded in reducing prednisolone to 5 mg (original maintenance dosage) without any recurrences (Fig. 1). To date, there has been no flare-up of scleritis for 12 months. Onset of scleritis during etanercept therapy. (Top left) 3 month after restarting etanercept retreatment, her scleritis was exacerbated. (Top right) The scleritis was completely limited 3 months after increasing the prednisolone dosage up to 30 mg/day without etanercept (middle left). The scleritis recurred 6 weeks after the second restart of etanercept treatment with 10 mg of prednisolone (middle right). The scleritis was completely reduced 3 months after increasing the prednisolone dosage up to 30 mg/day without etanercept (Bottom left). Two months after beginning infliximab and methotrexate treatment, we succeeded in reducing prednisolone to 5 mg (original maintenance dosage) without any recurrences (Bottom right). According to previous reports, TNF-α may play a role in uveitis and scleritis in patients with RA (Di Girolamo et al. 1997; Braun et al. 2005; Smith et al. 2005), but anecdotal reports paradoxically implicated etanercept as a cause of uveitis and scleritis (Lim et al. 2007; Le Garrec et al. 2009). On the other hand, another anti-TNF medication, infliximab, is effective in controlling eye involvements (Braun, et al. 2005). Our case suggests that etanercept may induce intractable scleritis or is ineffective in treating scleritis. Switching anti-TNF treatment from etanercept to infliximab was effective in controlling both RA and scleritis. The discrepancy of efficacy in the treatment of eye involvements might come from the mechanisms of these anti-TNF medications. Infliximab can bind to transmembrane forms of TNF-α, resulting in a breaking down of TNF-α-producing cells, while etanercept cannot affect TNF-α-producing cells because of its lack of binding to transmembrane forms of TNF. Our report does not suggest that infliximab should be preferred over etanercept in treatment of patients with inflammatory disease that may or may not be associated with eye involvements. However, if a patient has scleritis during etanercept therapy, then a change to infliximab therapy may be valuable.

Therapeutic Effect of Stealth-Type Polymeric Nanoparticles with Encapsulated Betamethasone Phosphate on Experimental Autoimmune Uveoretinitis

The therapeutic effects of betamethasone phosphate (BP) encapsulated in biocompatible and biodegradable blended nanoparticles of poly(lactic acid) (PLA) homopolymers and PEG-block-PLA copolymers (stealth nanosteroids) were examined in an experimental autoimmune uveoretinitis (EAU) model in Lewis rats. EAU was induced by S-antigen peptide in Lewis rats. Accumulation of systemically administered Cy7-labeled stealth nanoparticles in inflamed eyes of rats with EAU was assessed using in vivo fluorescence imaging, and the therapeutic effect of stealth nanosteroids, nonstealth nanosteroids, or saline on EAU was examined. The eyes were obtained 7 days after the treatment, and the histologic score was determined using pathologic findings. The expression of inflammatory cytokines including IL-6, IL-17, and VEGF was determined immunohistochemically. Cy7-stealth nanoparticles accumulated in inflamed eyes of rats with EAU and remained in situ for a 3-day period. Systemically administered stealth nanosteroids (100 μg of BP) reduced the clinical scores of rats with EAU within 1 day and maintained the effect for 2 weeks. This treatment also decreased the histologic scores and the expression of inflammatory cytokines in the retina of EAU. The strong therapeutic benefit on EAU obtained with the stealth nanosteroids may have been due to prolonged blood circulation and targeting to the inflamed uvea and retina, in addition to sustained release in situ.

Treatment of diffuse diabetic macular oedema using steroid eye drops

To evaluate the efficacy of treatment of diffuse diabetic macular oedema (DME) with difluprednate ophthalmic emulsion 0.05% (Durezol™) in eyes before vitrectomy. This study enrolled patients with diffuse DME for whom more than 3 months had passed since prior treatment. Nineteen eyes in 15 subjects were treated with difluprednate ophthalmic emulsion 0.05% four times daily for the first month and then twice daily for 2 months (treatment group). As a control group, 22 eyes in 11 subjects with DME were selected from subjects who underwent the steroid responder test. In the treatment group, the mean visual acuity (VA) (±SD) was 0.38 ± 0.25 logMAR and mean retinal thickness was 461.1 ± 109.9 μm at baseline. After 1 month of treatment, the mean VA had improved to 0.29 ± 0.25 (Wilcoxon rank-sum test, p = 0.30), while mean retinal thickness had decreased to 372.1 ± 70.0 μm (p = 0.006). The rate of effective improvement in retinal thickness was 42% and that of VA was 26%. In the control group, changes in neither VA nor retinal thickness were significant. Eye drop therapy using difluprednate ophthalmic emulsion 0.05% is a useful and effective treatment modality without surgical intervention or severe side-effects.

Pharmacokinetic Features of Difluprednate Ophthalmic Emulsion in Rabbits as Determined by Glucocorticoid Receptor-Binding Bioassay

Difluprednate (6α,9-difluoro-11β,17,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-acetate 17-butyrate, DFBA) has long been used as an anti-inflammatory dermatological agent. The main objectives of the current study were to evaluate the pharmacokinetic and pharmacodynamic features of DFBA when used as an ophthalmic agent, and to compare these features with those of other common ophthalmic agents, to determine which has the highest activity. A glucocorticoid (GC) receptor-binding test was performed to evaluate GC receptor-binding activity (GCRBA, the index of pharmacological effect). Using this information, we calculated dose-response curves, IC(50) values, and K(d) values to evaluate each drug's K(i) value. Finally, we performed studies in live rabbits to compare the activity of 4 formulations [0.002%, 0.01%, or 0.05% DFBA, or an ophthalmic solution of 0.1% betamethasone sodium phosphate (BMP)] at 4 time points (0.5, 1, 2, 4 h). At each time point, blood and eye samples were taken so that C(max) (the maximum equivalent concentration of the active DFBA metabolite, DFB), T(max) (the time at which C(max) was measured), and the area under the concentration-time curve could be compared across the 4 formulations. BMP had the highest K(i) value (8.4 × 10(-8) nmol/L), whereas DFB had the lowest (6.1 × 10(-11) nmol/L). The GCRBA of DFBA was intermediate to these 2 values (7.8 × 10(-10) nmol/L). Instillation of the DFBA ophthalmic emulsion in the eyes of rabbits led to dose-dependent increases in GCRBA, which was mostly attributable to the activity of DFB. The 0.05% DFBA ophthalmic emulsion elicited the greatest response in both aqueous humor and iris/ciliary body tissues, though there were no significant dose-dependent differences in GCRBA in plasma samples. The 0.05% DFBA ophthalmic emulsion appears to be an effective and safe anti-inflammatory treatment in ocular tissues. It is comparable, and possibly even superior, to the 0.1% BMP solution, and may be particularly useful in cases of severe disease where treatment with BMP solution alone is insufficient.

Stealth-Nanoparticle Strategy for Enhancing The Efficacy of Steroids in Mice with Noise-Induced Hearing Loss

This study aimed to investigate the efficacy of encapsulating steroids, which is a primary choice for the treatment of sensorineural hearing loss, in polyethylene glycol-coated polylactic acid nanoparticles for drug delivery to the cochlea. We prepared polyethylene glycol-coated polylactic acid nanoparticles encapsulating rhodamine or betamethasone phosphate (BP), and administered them systemically to CBA/N mice previously exposed to intense noise. We assessed nanoparticle distribution using rhodamine fluorescence, BP concentrations in tissues, nuclear translocation of glucocorticoid receptors and the function and histology of the mouse cochleae. Polyethylene glycol-coated polylactic acid nanoparticles delivered BP to cochleae over a sustained period, resulting in significant reductions in histological and functional damage to cochleae and indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of BP in acute sensorineural hearing loss.