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Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity

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Abstract

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations’ inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.

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Data Availability

The corresponding author will provide the datasets created during and/or analyzed during the current investigation upon reasonable request.

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Acknowledgements

The authors would not neglect to thank both Yeditepe University Faculty of Genetic and Bioengineering and Yeditepe University Faculty of Chemical Engineering for their unconditional permission analyses throughout the project period. Especially, authors would like to express their deepest gratitude in-person to Dr. Ebru Turkoz Acar, Dr. Manolya Hatipoglu, Dr. Cem Levent Altan, and Beyza Abisoglu.

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Authors and Affiliations

  1. Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey

    Burcu Uner

  2. Faculty of Pharmacy, Yeditepe University, Atasehir, 34755, Istanbul, Turkey

    Burcu Uner & Cetin Tas

  3. University of Health Science and Pharmacy in St. Louis, 1 Pharmacy Place, St. Louis, Missouri, 63110-1088, USA

    Burcu Uner

  4. Faculty of Pharmacy, Istanbul Health and Technology University, Zeytinburnu, 34010, Istanbul, Turkey

    Samet Ozdemir

  5. Faculty of Pharmacy, Istanbul University, Beyazıt, 34116, Istanbul, Turkey

    Melike Uner & Yildiz Ozsoy

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Contributions

Burcu Uner contributed to the investigation, software, methodology, and editing and writing of original manuscript. Samet Ozdemir contributed to the investigation, validation, and review. Yildiz Ozsoy, Melike Uner, and Cetin Tas contributed to the supervision, writing, and review.

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Correspondence to Burcu Uner.

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Uner, B., Ozdemir, S., Tas, C. et al. Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity. AAPS PharmSciTech 24, 92 (2023). https://doi.org/10.1208/s12249-023-02551-6

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