Ocular irritation and cyclosporine A distribution in the eye tissues after administration of Solid Lipid Microparticles in the rabbit model

Wolska, Eliza; Sznitowska, Małgorzata; Chorążewicz, Juliusz; Szerkus, Oliwia; Radwańska, A; Markuszewski, Michał J.; Kaliszan, Roman; Raczyńska, Krystyna

doi:10.1016/j.ejps.2018.05.015

Cited by 12 publications

(21 citation statements)

References 47 publications

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“…The calculated eye irritation score in CL10 was 0.50, while it was 0.17 in the reference. The irritation score observed in CL10 was relatively low and could be classified as practically non-irritant [57]. Further, instillation of CL10 did not cause redness, swelling, or excessive lachrymation in the eye.…”

Section: Ocular Compatibilitymentioning

confidence: 85%

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

et al. 2021

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Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

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Section: Ocular Compatibilitymentioning

confidence: 85%

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

et al. 2021

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“…SLM are multicompartment drug carriers that allow for the prolonged release of API with the aim to increase its effectiveness [ 8 , 38 ]. As was previously reported [ 38 ], SLM dispersion with 2% of CsA was characterized by a two-stage release profile: rapid and prolonged, which resulted from the specific distribution of CsA; it was localized mainly on the lipid surface, not being fully incorporated into the lipid core [ 8 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…The drug-loaded formulations contained 0.1% or 1.0% ( w/w ) of CsA and 0.1% or 0.5% ( w/w ) of SPIR. All the SLM formulations contained 10% ( w/w ) of a lipid phase and were prepared using a hot emulsification method, as previously reported [ 8 , 38 ]. The mixing process of the lipid phase with the aqueous phase was performed at 80 °C using a high-shear mixer Ultra-Turrax (T25 Janke-Kunkel, IKA Labortechnik, Staufen, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…The analysis of SLM dispersions was performed as described previously [ 8 , 38 ]. The SLM were observed using the optical microscope (Nikon Eclipse 50i, Nikon Corporation, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Distribution of CsA or SPIR between the aqueous phase and the lipid core was assessed as described previously [ 8 , 38 ]. The fraction of free drug dissolved in the aqueous phase of the SLM dispersion was determined after ultrafiltration.…”

Section: Methodsmentioning

confidence: 99%

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Analytical Techniques for the Assessment of Drug-Lipid Interactions and the Active Substance Distribution in Liquid Dispersions of Solid Lipid Microparticles (SLM) Produced de novo and Reconstituted from Spray-Dried Powders

et al. 2020

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Solid lipid microparticles (SLM) can be presented as liquid suspension or spray-dried powder. The main challenge in SLM technology is to precisely determine the location of the active substance (API) in the different compartments of the formulation and its changes during SLM processing. Therefore, the purpose of the research was to assess the distribution of the API and to investigate the nature of the API-lipid interaction when the formulation was subjected to spray drying, with an indication of the most suitable techniques for this purpose. SLM were prepared with two various lipids (Compritol or stearic acid) and two model APIs: cyclosporine (0.1% and 1% w/w) and spironolactone (0.1% and 0.5% w/w). Physicochemical characterizations of the formulations, before and after spray drying, were performed by differential scanning calorimetry (DSC), atomic force microscopy (AFM), Raman spectroscopy and nuclear magnetic resonance (NMR). The API distribution between the SLM matrix, SLM surface and the aqueous phase was determined, and the release study was performed. It was demonstrated that, in general, the spray drying did not affect the drug release and drug distribution; however, some changes were observed in the SLM with Compritol and when the API concentration was lower. Only in the SLM with stearic acid was a change in the DSC curves noted. Measurements with the AFM technique proved to be a useful method for detecting differences in the surface properties between the placebo and API-loaded SLM, while the Raman spectroscopy did not show such evident differences.

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Microparticle Products for the Eye: Preformulation, Formulation, and Manufacturing Considerations

Andrés‐Guerrero

Molina‐Martínez

Bravo‐Osuna

et al. 2021

Ophthalmic Product Development

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Ocular irritation and cyclosporine A distribution in the eye tissues after administration of Solid Lipid Microparticles in the rabbit model

Cited by 12 publications

References 47 publications

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Analytical Techniques for the Assessment of Drug-Lipid Interactions and the Active Substance Distribution in Liquid Dispersions of Solid Lipid Microparticles (SLM) Produced de novo and Reconstituted from Spray-Dried Powders

Microparticle Products for the Eye: Preformulation, Formulation, and Manufacturing Considerations

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