Search

Purpose: The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections.Methods: The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex®). Histological evaluation was performed in bovine corneas to assess the safety of microemulsion in comparison to Tobradex suspension. In addition, the stability of the microemulsion was studied at 4°C, 25°C, and 40°C.Results: The pH of the microemulsion was close to the pH of tear fluid. The microemulsion displayed an average globule size under 20 nm, with light transmittance around 95%-100%. The aseptically prepared microemulsion remained sterile for up to 14 days. The cytotoxicity of the microemulsion in bovine corneal endothelial cells was comparable to that of the Tobradex suspension. The anti-inflammatory activity of dexamethasone and the antibacterial activity of tobramycin from the microemulsion were significantly higher than those of the Tobradex suspension (P < 0.05). Histological evaluation showed an intact corneal epithelium without any signs of toxicity, and the developed microemulsion was found to be stable at 4°C and 25°C for 3 months.Conclusion: In conclusion, the developed microemulsion could be explored as a suitable alternative to the marketed suspension for treating anterior segment eye infections. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to develop and characterize a novel sustained-release drug delivery system of cyclosporine-A (CsA) using hydroxypropyl methylcellulose (HPMC) and xanthan gum (XG) for treating dry eye disease (DED).Methods: Polymeric inserts of CsA were prepared using the solvent casting technique with a 2(3) full factorial design to evaluate the effect of HPMC and XG ratios and drug content on thickness, folding endurance, wettability, and in vitro drug release. Inserts were also evaluated for drug content, moisture absorption and loss, and surface pH. Inserts with an optimized ratio of HPMC and XG were sterilized with UV light and evaluated for morphology, thermal analysis, Fourier transform infrared spectroscopy, stability at 4°C, 25°C, and 40°C, cytotoxicity in cultured bovine corneal endothelial cells, and anti-inflammatory effect in Jurkat T cells.Results: The addition of XG increased the CsA release duration and enhanced the folding endurance of films. All films showed uniformity in drug content and thickness. Formulation F4 composed of 1% HPMC and 0.25% XG exhibited good folding endurance and sustained CsA release for up to 20 h. Sterility testing of F4 using plate and direct inoculation confirmed the formulation sterility and validated the sterilization method. The formulation was stable for at least 3 months at 4°C, 25°C, and 40°C. No cytotoxicity was observed in cultured bovine corneal endothelial cells for up to 24 h. The anti-inflammatory effect of CsA was intact in ophthalmic inserts.Conclusion: In conclusion, combination therapy with HPMC and CsA can be a potential once-a-day formulation for treating DED. [ABSTRACT FROM AUTHOR]

Purpose: This study aims at the development and preliminary evaluation of dexamethasone nanomicelles for treating posterior uveitis. Nanomicelles were formulated using polyoxyl 40 stearate (P40S) and polysorbate 80 (P80), which are approved by the FDA for ocular use. Methods: Dexamethasone nanomicelles were prepared and characterized for critical micellar concentration, solubility of dexamethasone, particle size, surface charge, morphology, in vitro drug release, clarity, stability, filtration efficiency, and sterility. Ocular tolerance and the tissue drug distribution of dexamethasone were assessed in rabbits after single and multiple topical administration. Results: Dexamethasone nanomicelles (0.1% w/v) were successfully developed and characterized with an optimized composition of P40S/P80=7/3 by weight. The mean diameter of blank and drug-loaded nanomicelles was 13.3±0.4 and 14.5±0.4 nm, respectively. Transmission electron microscopy images revealed the spherical structure of nanomicelles. Nanomicelles were found to be stable with respect to clarity, size and drug content at 4°C and 25°C for up to 6 months. No irritation or redness was observed in the treated eyes as compared with the untreated control rabbit eyes. Therapeutic concentrations of dexamethasone were observed in the retina and choroid after single and multiple topical application in rabbits. Conclusion: In conclusion, the nanomicelles of P40S and P80 could efficiently solubilize 0.1% dexamethasone in their cores. The results also indicate that mixed nanomicelles could be utilized as a potential delivery system for delivering dexamethasone to treat the back of the eye diseases such as posterior uveitis after topical application. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valine-D-valine-ACV, D-valine-L-valine-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Methods: Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-co-glycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. Results: L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of L-valine-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Conclusion: Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using doxorubicin (DOX) as a model drug. Methods: Biodegradable DOX-loaded poly(,-lactide- co-glycolide)-poly(ethylene glycol)-folate (PLGA-PEG-FOL) micelles (DOXM) were prepared with various solvents (dimethylsulfoxide, acetone, and dimethylformamide). The effects of solvents on entrapment efficiency, particle size, and polydispersity were examined. The effects of thermosensitive gel structure on the release of DOX from the DOXM were also studied. Qualitative and quantitative uptake studies of DOX and DOXM were carried out in Y-79 cell line. Cytotoxicity studies of DOXM were performed on Y-79 cells. Results: Based on size, polydispersity, and entrapment efficiency, dimethylformamide was found to be the most suitable solvent for the preparation of DOXM. Dispersion of DOXM in PLGA-PEG-PLGA gel sustained drug release for a period of 2 weeks. Uptake of DOX was ∼4 times higher with DOXM than DOX in Y-79 cells overexpressing folate receptors. This was further confirmed from the quantitative uptake studies. DOXM exhibited higher cytotoxicity in Y-79 cells when compared with pure DOX. Conclusion: These polymeric micellar systems suspended in thermosensitive gels may provide sustained and targeted delivery of anticancer agents to retinoblastoma cells following intravitreal administration. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the role of sodium-dependent multiple vitamin transporter (SMVT) on Biotin-Ganciclovir (biotin-GCV) uptake on both human retinal pigmented epithelium cell line (ARPE-19) and rabbit retina. Study also aims to delineate the vitreal pharmacokinetics of biotin-GCV. Method: ARPE-19 was employed to study the in vitro uptake experiments. New Zealand white albino rabbits were used to study in vivo retinal uptake and vitreal pharmacokinetics following intravitreal administration of biotin-GCV. In vitro uptake kinetics of [3H] biotin was determined at various initial concentrations. Competitive inhibition studies were conducted in the presence of unlabelled biotin, desthiobiotin, pantothenic acid, and lipoic acid. Various other uptake studies were performed to functionally characterize the transporter. To provide the molecular evidence of this transporter, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) studies were also conducted. In vivo retinal/choroidal uptake studies were carried out with New Zealand albino rabbits. Unconscious animal ocular microdialysis studies were performed in order to evaluate intravitreal pharmacokinetics of GCV and Biotin-GCV. Results: Uptake of [3H] biotin into ARPE-19 was linear over 7min, and found to be saturable with Km of 138.25 μM and Vmax of 38.85 pmol/min/mg protein. Both pantothenic acid and lipoic acid decreased significantly in uptake of biotin in the concentration-dependent manner. Uptake of biotin into ARPE-19 was found to be temperature, energy, and Na+ dependent but Cl−independent. Further, RT-PCR studies identified a band exhibiting presence of hSMVT on ARPE-19. Biotin-GCV is recognized by SMVT system present on the ARPE-19 and rabbit retina. Vitreal Pharmacokinetics profile reveals that most of the parameters were not significantly different for GCV and Biotin-GCV. However, use of Biotin-GCV may result in sustain levels of regenerated GCV in vitreous. Conclusions: SMVT was identified and functionally characterized on ARPE-19 cells. Further, Biotin-GCV shares this transport system. Vitreal pharmacokinetics of the conjugate was determined in unconscious rabbit model. [ABSTRACT FROM AUTHOR]