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. 2022 Jan 26;14(2):285.
doi: 10.3390/pharmaceutics14020285.

Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation

Ruth Galindo  1   2 , Elena Sánchez-López  1   2   3   4 , María José Gómara  2 , Marta Espina  1   3 , Miren Ettcheto  4   5 , Amanda Cano  1   3   4 , Isabel Haro  2 , Antoni Camins  4   5 , María Luisa García  1   3   4
Affiliations

Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation

Ruth Galindo et al. Pharmaceutics. .

Abstract

Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed. Additionally, to avoid fast clearance and increase cellular internalization into the ocular tissues, PLGA nanoparticles have been functionalized using PEG and cell penetrating peptides (Tet-1 and B6). To optimize the formulations, a factorial design was carried out and short-term stability of the nanoparticles was studied. Moreover, morphology was also observed by transmission electron microcopy and in vitro drug release was carried out. Ocular tolerance of the formulations was ensured in vitro and in vivo and anti-inflammatory therapeutic efficacy was also assessed. Surface functionalized nanoparticles loading Licochalcone-A were developed with an average size below 200 nm, a positive surface charge, and a monodisperse population. The formulations were non-irritant and showed a prolonged Licochalcone-A release. Despite the fact that both Licochalcone-A Tet-1 and B6 functionalized nanoparticles demonstrated to be suitable for the treatment of ocular inflammation, B6 targeted nanoparticles provided greater therapeutic efficacy in in vivo assays.

Keywords: Licochalcone-A; PLGA; cell-penetrating peptides; nanoparticles; ocular inflammation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Conjugation of PEG and cell penetrating peptides (CPPs) to PLGA and preparation of Lico-A PLGA-PEG-CPP NPs.
Figure 2
Figure 2
Design of experimental results. (A) Surface response plot for Zav, (B) Surface response plot for PI, (C) Pareto chart for EE (A: Lico-A concentration; B: PLGA concentration; C: Tween concentration; vertical blue line indicates significant effect), (D) Contoured surface response plot for EE.
Figure 3
Figure 3
Turbiscan backcattering profile at different temperatures analyzed monthly. (A) 4 °C, (B) 25 °C and (C) 38 °C.
Figure 4
Figure 4
Transmission electron microscopical images of Lico-A NPs. (A) Lico-A-PLGA NPs (scale bar corresponds to 1 µm), (B) Lico-A PLGA-PEG-Tet-1 NPs (scale bar corresponds to 100 nm), and (C) Lico-A PLGA-PEG-B6 NPs (scale bar corresponds to 500 nm).
Figure 5
Figure 5
Lico-A release profile carried out by direct dialysis method for studying several formulations (Lico-A PLGA NPs, Lico-A PLGA-PEG-Tet1 NPs, and Lico-A-PLGA-PEG-B6 NPs).
Figure 6
Figure 6
HET-CAM assessment images after 5 min of the product application. (A) NaCL, (B) NaOH, (C) SDS 1%, (D) Lico-A PLGA NPs, (E) Lico-A PLGA-PEG-Tet-1 NPs, (F) Lico-A PLGA-PEG-B6 NPs.
Figure 7
Figure 7
Ocular anti-inflammatory results. (A) Ocular inflammation score. (B) Inhibition of inflammation (%). Significant differences compared to the saline serum group: ** p < 0.01; *** p < 0.005; **** p < 0.0001.
Figure 7
Figure 7
Ocular anti-inflammatory results. (A) Ocular inflammation score. (B) Inhibition of inflammation (%). Significant differences compared to the saline serum group: ** p < 0.01; *** p < 0.005; **** p < 0.0001.
See this image and copyright information in PMC

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