Development of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loteprednol Etabonate: Physicochemical Characterization and Ex Vivo Permeation Studies

Purpose Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye, and management of seasonal allergic rhinitis nasally. LE which is a poorly soluble drug with insufficient bioavailability, has a high binding affinity to steroid receptors. Sophisticated colloidal drug delivery systems of LE could present an alternative for treatment of inflammatory and allergic conditions of the skin. For this purpose, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve for transdermal LE delivery for the first time. Methods SLN and NLC were produced by hot homogenization and ultrasonication technique. Formulations were characterized by dynamic light scattering, scanning electron microscopy, fourier transform infrared spectroscopy and differential scanning calorimetry. Their physical stability was monitored for 3 months of storage. Drug release profiles and permeation properties of SLN and NLC through the porcine skin were investigated. Results It was determined that SLN and NLC below 150 nm particle size had a homogeneous particle size distribution as well as high drug loading capacities. They were found to be stable both physically and chemically at room temperature for 90 days. In terms of release kinetics, it was determined that they released from SLN and NLC in accordance with Fickian diffusion release. Formulations prepared in this study were seen to significantly increase drug penetration through pig skin compared to the control group (p ≤ 0.05). Conclusion SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with less side-effect profile in the treatment of inflammatory problems on the skin.

COMPARATIVE STUDY OF THE EFFICACY OF TOPICAL LOTEPREDNOL ETABONATE AND FLUOROMETHOLONE IN THE TREATMENT OF VERNAL KERATOCONJUNCTIVITIS : A RANDOMISED CONTROLLED STUDY

Introduction:Vernal keratoconjunctivitis(VKC) is a chronic, recurrent, inammatory disease of ocular surface showing seasonal exacerbation, affecting young children. Topical steroids are the mainstay in the treatment of ocular allergy, but their use should be judicious since they carry serious side effects . Loteprednol and uorometholone carry better safety prole. Present study was conducted with the aim of comparing the efcacy of these two widely used steroids.Objectives:To compare total subjective symptom score (TSSS), total objective sign score (TOSS) and side effects of medications before and after treatment at each visit.Materials & Methods:A prospective randomised controlled study was performed on 92 patients of VKC over four weeks. Patients were allotted to either of the two arms of treatment (i.e. LP 0.5% or FML 0.1%). Subjective and objective assessments of the signs and symptoms of VKC were done using standard scoring methodologies at 7, 14, 21 and 28 days post treatment. The main outcome measure was measured in terms of TSSS and TOSS before and after treatment at each visit. Secondary outcomes included side effects. Statistical analysis of the data collected was carried out.Results: Loteprednol showed greater reduction in symptoms initially but by the end of study there was no statistically signicant difference in effect between the two drugs.Conclusions: Final improvement in clinical features and safety prole, at the end of 4 weeks was similar in eyes treated with either of the two drugs. Hence, both the drugs can be safely used in the treatment of VKC.

Improved accuracy of intraocular lens power calculation by preoperative management of dry eye disease

Background To evaluate the effects of pretreatment for dry eye disease (DED) on the accuracy of intraocular lens (IOL) power calculation. Methods Patients who underwent uneventful cataract surgery were included in the study. IOL power was determined using the SRK/T and Barrett Universal II (Barrett) formulas. The patients were divided into non-pretreatment and pretreatment groups, and those in the pretreatment group were treated with topical 0.5% loteprednol etabonate and 0.05% cyclosporin A for 2 weeks prior to cataract surgery. Ocular biometry was performed in all groups within 2 days before surgery. The mean prediction error, mean absolute error (MAE), and proportions of refractive surprise were compared between the non-pretreatment and pretreatment groups at 1 month postoperatively. Refractive surprise was defined as MAE ≥ 0.75D. Results In a total of 105 patients, 52 (52 eyes) were in the non-pretreatment group and 53 (53 eyes) in the pretreatment group. The MAE was 0.42 ± 0.33, 0.38 ± 0.34 (SRK/T, Barrett) and 0.23 ± 0.19, 0.24 ± 0.19 in the non-pretreatment and pretreatment groups, respectively (p < 0.001/=0.008). The number of refractive surprises was also significantly lower in the pretreatment group. [non-pretreatment/pretreatment: 9/2 (SRK/T); 8/1 (Barrett); p = 0.024/0.016]. Pretreatment of DED was related to a reduction in postoperative refractive surprise. [SRK/T/Barrett: OR = 0.18/0.17 (95% CI: 0.05–0.71/0.05–0.60), p = 0.014/0.006]. Conclusions The accuracy of IOL power prediction can be increased by actively treating DED prior to cataract surgery.

Is there a role for tapered topical dose steroidal treatment for dry eye disease? A randomized, pilot study

Purpose: To evaluate the effect of tapered doses of loteprednol-etabonate in dry eye disease patients. Materials and methods: Dry eye and treatment outcomes were assessed by Schirmer I test, tear BUT, lissamine green conjunctival staining, fluorescein corneal staining, and HLA-DR expression on conjunctival cells. Patients received either loteprednol-etabonate 0.5% twice daily for 14 days tapered to once daily for 14 days, and then twice weekly for 28 days ( n = 10), or NaCl 0.9%. Results: A significant decrease of ocular surface inflammation and improvement of symptoms was recorded in the study group compared with controls at days 14 and 56. Change from baseline in HLA-DR expression in CD45+ conjunctival cells was significantly higher in treated patients at day 14. Intraocular pressure and best corrected visual acuity were preserved in all treated eyes. Conclusions: Tapered doses of loteprednol etabonate 0.5% suspension controlled ocular surface inflammation, improving dry eye symptoms.

KPI-121 1% for pain and inflammation in ocular surgery

Pain and inflammation are common experiences following ocular surgery and, if uncontrolled, can compromise patients’ vision, functioning and quality of life. Corticosteroid drugs are available to manage inflammation and discomfort but have limitations in penetrating the ocular mucus barrier to reach the target ocular tissues. KPI-121 1% (INVELTYS®) is a novel formulation of loteprednol etabonate that employs innovative proprietary technology to deliver nanoparticle-sized mucus-penetrating particles to the cornea. Results from clinical trials demonstrate that KPI-121 1% is effective and well tolerated. KPI-121 1% uses mucopenetrative technology for ophthalmic use and is the only US FDA-approved twice-daily ocular corticosteroid indicated for the treatment of inflammation and pain after ocular surgery.