Sorafenib Repurposing for Ophthalmic Delivery by Lipid Nanoparticles: A Preliminary Study

Abstract

Uveal melanoma is the second most common melanoma and the most common intraocular malignant tumour of the eye. Among various treatments currently studied, Sorafenib was also proposed as a promising drug, often administered with other compounds in order to avoid resistance mechanisms. Despite its promising cellular activities, the use of Sorafenib by oral administration is limited by its severe side effects and the difficulty to reach the target. The encapsulation into drug delivery systems represents an interesting strategy to overcome these limits. In this study, different lipid nanoparticulate formulations were prepared and compared in order to select the most suitable for the encapsulation of Sorafenib. In particular, two solid lipids (Softisan or Suppocire) at different concentrations were used to produce solid lipid nanoparticles, demonstrating that higher amounts were able to achieve smaller particle sizes, higher homogeneity, and longer physical stability. The selected formulations, which demonstrated to be biocompatible on Statens Seruminstitut Rabbit Cornea cells, were modified to improve their mucoadhesion, evaluating the effect of two monovalent cationic lipids with two lipophilic chains. Sorafenib encapsulation allowed obtaining a sustained and prolonged drug release, thus confirming the potential use of the developed strategy to topically administer Sorafenib in the treatment of uveal melanoma.

Optimization of Lipid Nanoparticles by Response Surface Methodology to Improve the Ocular Delivery of Diosmin: Characterization and In-Vitro Anti-Inflammatory Assessment

“…The chosen lipids, Softisan 100, Capryol 90, and Gelucire 44/14, were conceived by evaluating the literature of recent years. In particular, some recent works in ophthalmic drug delivery have been published on these materials [31][32][33]. The choice of one solid lipid over another will be a matter of choice during DoE (design of experiments).…”

“…Further evidence of this was obtained when the D-NLC system was destroyed by methanol and re-analyzed: at this point the diosmin peaks were visible. In the spectra of Softisan ® 100, NLCs, D-NLCs, and destroyed D-NLCs the typical Softisan ® 100 peaks were noted, with characteristic absorption bands related to C-H stretching of benzene (2800-2955 cm −1 ), carbonyl compound CHO (1728, 1739 cm −1 ), C-O stretching (1000-1300 cm −1 ) [31]. Additionally, Capryol ® 90 typical peaks were identified at 3432 (O-H), 2925-2859 (aliphatic C-H), and 1728 (C=O) cm −1 .…”

Almond oil O/W nanoemulsions: Potential application for ocular delivery

“…To deeply investigate NE mucoadhesive behavior, mucin particle method was performed. It is a general test useful for the preliminary evaluation of mucoadhesive properties of materials and/or nanocarriers by measuring variation in HD and ZP after incubation with mucin glycoprotein [61,62]. Particle-mucin interactions were furtherly confirmed by ZP and HD measurements.…”

Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms

“…Sterile filtration has also been exploited as a sterilization approach for lipid nanoparticles used in ophthalmic application, as described by Bonaccorso et al [ 157 ]. The authors investigated the influence of different types of membranes (polypropylene, polyethylene sulfone, polyvinylidene fluoride; pore size of 0.22 µm) on the filtration feasibility of sorafenib-loaded SLNs.…”