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. 2021 Aug 2;26(15):4673.
doi: 10.3390/molecules26154673.

Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence

Carmelo Puglia  1   2 , Debora Santonocito  1 , Giuseppe Romeo  1 , Sebastiano Intagliata  1 , Giovanni Luca Romano  3   4 , Enrica Strettoi  5 , Elena Novelli  5 , Carmine Ostacolo  6 , Pietro Campiglia  7 , Eduardo Maria Sommella  7 , Rosario Pignatello  1   2 , Claudio Bucolo  3   4
Affiliations

Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence

Carmelo Puglia et al. Molecules. .

Abstract

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.

Keywords: fluorescence microscopy; fluorescent nanoparticle; nanomedicine; ocular drug delivery; retina.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
ODAF structure (lactone form).
Figure 2
Figure 2
Transmission electron microscopy images of LN-ODAF. The scale bar represents 200 nm.
Figure 3
Figure 3
LN-ODAF diffusion to ocular structures. (A–D) Progressive invasion of the green fluorescence signal in time. C: cornea; ON: optic nerve; R: retina; S: sclera. L: Lens. Asterisks in (A,C) indicate periocular structures abutting areas of bright fluorescent staining of the underlying retina, suggesting outer-to-inner diffusion at focal points.
See this image and copyright information in PMC

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