We report two patients who developed toxic keratopathy following high-dose cytarabine chemotherapy and whose symptoms resolved following topical loteprednol etabonate 0.5% treatment. A 25-year-old woman and a 26-year-old man with acute myeloid leukemia were referred to our department with symptoms of ocular discomfort, photophobia, and blurred vision after consolidation chemotherapy. Central corneal epithelial microcysts were observed bilaterally in both patients, and in vivo confocal microscopy showed highly reflective disseminated granular and irregular intraepithelial opacities, mainly in the basal epithelial layers. Loteprednol etabonate 0.5% relieved both patients' symptoms in less than a week, and the microcysts disappeared in 2 to 3 weeks of treatment. Although there is no standardized treatment protocol for cytarabine-induced corneal toxicity, dexamethasone 0.1% and prednisolone phosphate 1.0% were reported to be effective in the resolution of discomfort and symptoms. In the two patients we report herein, loteprednol etabonate 0.5% four times daily was also effective in suppressing the symptoms.

Influenza viruses can cause severe life threatening infections in high-risk patients, including young children, the elderly and patients with compromised immunity due to underlying medical conditions or immunosuppressive treatment. The impaired immunity of these patients causes prolonged virus infection and combined with antiviral treatment facilitates the emergence of viruses with resistance mutations. The diverse nature of their immune status makes them a challenging group to study the impact of influenza virus infection and the efficacy of antiviral therapy. Immunocompromised ferrets may represent a suitable animal model to assess influenza virus infection and antiviral treatment strategies in immunocompromised hosts. Here, ferrets were given a daily oral solution of mycophenolate mofetil, tacrolimus and prednisolone sodium phosphate to suppress their immune system. Groups of immunocompromised and immunocompetent ferrets were inoculated with an A/H3N2 influenza virus and were subsequently treated with Oseltamivir or left untreated. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed on the throat and nose specimens to study virus replication during the course of infection. All immunocompromised ferrets had prolonged presence of viral RNA and a higher total amount of virus shedding compared to the immunocompetent ferrets. Although Oseltamivir reduced the total amount of virus shedding from the nose and throat of treated ferrets, it also resulted in the emergence of the neuraminidase R292K resistance substitution in all these animals, as determined by mutation specific RT-PCR and next-generation sequencing. No additional mutations that could be associated with the emergence of the R292K resistance mutation were detected. The immunocompromised ferret model can be used to study A/H3N2 virus shedding and is a promising model to study new antiviral strategies and the emergence of antiviral resistance in immunocompromised hosts.

The objective of the present study was to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin hydrochloride, and prednisolone sodium phosphate. Melt-cast method was used to fabricate ophthalmic inserts. Polyethylene oxide N10, a semicrystalline thermoplastic polymer (polyethylene oxide N10; Mol. wt: 100 kDa) was used as the matrix-forming material. Polymeric insert units (4 × 2 × 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability, and in vivo ocular tissue distribution. Marketed ophthalmic solutions were used as control solutions. Drug content in all the formulations ranged between 93% and 102% of the theoretical value. Transmembrane flux of IN, prednisolone sodium phosphate, and ciprofloxacin hydrochloride was enhanced by ∼3.5-folds, ∼3.6-folds, and ∼2.9-folds, respectively, from the polymeric inserts compared with the control formulations, after 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, compared with their control formulations. The melt-cast ophthalmic inserts show promise as an effective noninvasive ocular drug delivery platform, which will be highly beneficial in the intervention and treatment of a wide variety of ocular complications.

Niosomes embodying ethanol and minimum amount of cholesterol (ethoniosomes) could be promising ocular delivery systems for water soluble and insoluble drugs. This manuscript reports on novel nano-sized elastic niosomes (ethoniosomes) composed of Span 60: cholesterol (7:3 mol/mol) and ethanol, for ocular delivery of prednisolone acetate (Pred A) and prednisolone sodium phosphate (Pred P). These ethoniosomes were prepared with the thin film hydration (TFH) and ethanol injection (EI) methods, characterized for percentage entrapment efficiency (% EE), size, zeta potential, morphology, elasticity, in vitro release and physical stability. Ocular irritation, bioavailability and anti-inflammatory effects were evaluated and compared with the conventional suspension and solution eye drops. The prepared ethoniosomal vesicles (EV) had a Z-average diameter of 267 nm, zeta potential of approximately -40 mV and % change in size after extrusion of 4%. They were physically stable for at least 2 months at 4 °C. The prepared EV showed good ocular tolerability using the modified Draize's test and the estimated relative ocular bioavailability for Pred A EV and Pred P EV was 1.54 and 1.75 times greater than that for the suspension and solution eye drops, respectively. The time required for complete healing from the clove oil-induced severe ocular inflammation was reduced to half with Pred A and Pred P EV. More interestingly, the intraocular pressure (IOP) elevation side effect recorded for Pred A and Pred P EV was significantly less than that for the conventional suspension and solution eye drops.

In this study it was investigated whether hydroxypropyl-β-cyclodextrin (HPβCD) is able to stabilize the liposomal membranes during drying of long circulating polyethylene glycol (PEG) coated liposomes, as compared to the disaccharides trehalose and sucrose. PEGylated liposomes loaded with prednisolone disodium phosphate (PLP) were dried by spray-drying or freeze-drying. The dried powders were tested on their residual moisture content, glass transition temperature and amorphous character. Upon reconstitution the liposomal size, size distribution and drug retention were determined and the results were compared to the characteristics of the formulation solution before drying. In contrast to the disaccharides, HPβCD stabilizes the liposomal membranes of the PEGylated liposomes during the drying process of both spray drying and freeze-drying when present in a lipid:carbohydrate ratio of 1:6 (w/w). The resulting powder can be stored at room temperature. No changes in size and size distribution were seen upon reconstitution of the HPβCD containing formulations. Drying resulted in a minimal leaking of PLP from the liposomes. Its relatively high [Formula: see text] and T(g) of HPβCD, as compared to the disaccharides, make HPβCD an excellent membrane protectant for dry PEGylated liposomal formulations.

Capsular contracture is a potential adverse effect of breast implants. An inflammatory reaction is most likely the origin of fibrosis around the implant. It is possible that some substances may act to prevent this inflammatory reaction. Thus, our goal was to evaluate the effectiveness of local depot prednisolone phosphate-liposomes (PPL) on fibrous capsule formation around textured silicone breast implants. Shell prostheses (2 mL) were implanted in the right (plus PPL group) and left (plus saline solution, saline group) subcutaneous dorsum of 18 rats. In another 18 rats, the implants were positioned in the left of the back without any drug instillation (control group). In the PPL group, the capsule thickness (microm) and density (%) of collagen were significantly (p<0.0001) lower compared with the control group on days 35 and 90 postsurgery. Furthermore, in the PPL group, a significant reduction in myofibroblast count was observed on day 90 postsurgery (p<0.0001). In conclusion, a single dose of depot liposome-delivered prednisolone was effective at impairing capsule formation around the silicone implant. The results suggest a strong local and weak systemic effect of PPL on the fibrous tissue around silicone implants. To our knowledge, no study has yet assessed the effect of PPL on silicone breast implants.

The objective of the present study was to investigate the effect of topically coadministered P-glycoprotein (P-gp) substrates/inhibitors on the vitreal kinetics of a systemically administered P-gp substrate. Anesthetized male rabbits were used in these studies. The concentration-time profile of quinidine in the vitreous humor, after intravenous administration, was determined alone and in the presence of topically coadministered verapamil, prednisolone sodium phosphate (PP), and erythromycin. The vitreal pharmacokinetic parameters of quinidine in the presence of verapamil [apparent elimination rate constant (λ(z)), 0.0027 ± 0.0002 min(-1); clearance (CL_F), 131 ± 21 ml/min; area under the curve (AUC(0-∞)), 39 ± 7.0 μg · min/ml; and mean residence time, 435 ± 20 min] were significantly different from those of the control (0.0058 ± 0.0006 min(-1), 296 ± 46 ml/min, 17 ± 3 μg · min/ml, and 232 ± 20 min, respectively). A 1.7-fold decrease in the vitreal λ(z) and a 1.5-fold increase in the vitreal AUC of quinidine were observed in the presence of topical PP. Statistically significant differences between the vitreal profiles of the control and erythromycin-treated group were also observed. Plasma concentration-time profiles of quinidine, alone or in the presence of the topically instilled compounds, remained unchanged, indicating uniform systemic quinidine exposure across groups. This study demonstrates an interaction between topically and systemically coadministered P-gp substrates, probably through the modulation of P-gp on the basolateral membrane of the retinal pigmented epithelium, leading to changes in the vitreal kinetics of the systemically administered agent.

Formulation of a new Prednisolone acetate (1%) ophthalmic suspension to obtain a better contactibility of the drug at the site of action. The formulation was evaluated and optimized based on physiological, physicochemical and pharmaceutical parameters and prepared aseptically, keeping particle size between 1-3 microm, while viscosity enhancer, preservative, chelating agent were used to increase the transient residence time, antimicrobial preservation respectively. Isotonicity of the formulation was maintained. Buffering agents used were having buffering capacity NMT 0.05%. pH adjusted at which Prednisolone acetate was stable. The finished product subjected to stress conditions to check the physical stability of the formulation. The formulation was packed in LDPE plastic vials, and subjected to accelerated stability studies at 40 degrees C and the kinetic and predictive method was employed for the determination of degradation rate constant and shelf life. The results showed that the development of a new ophthalmic formulation having significantly better contact time by the selection and optimization of viscosity (HPMC) that obtained (21 cps) with better stability studies. The results concluded that prednisolone acetate 1.0 per cent ophthalmic suspension is more effective than prednisolone phosphate 1.0 per cent ophthalmic solution in suppressing corneal inflammation.