Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec;26(1):952-964.
doi: 10.1080/10717544.2019.1667451.

Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment

Wang Xingqi  1 , Zhang Yong  1 , Li Xing  1 , Wang Yang  1 , Huang Jie  1 , Hu Rongfeng  1   2 , Gui Shuangying  1   2 , Chu Xiaoqin  1   2
Affiliations

Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment

Wang Xingqi et al. Drug Deliv. 2019 Dec.

Abstract

The objective of this work was to investigate phytantriol-based liquid crystal (LC) gels including cubic (Q2) and hexagonal (H2) phase for ocular delivery of pilocarpine nitrate (PN) to treat glaucoma. The gels were produced by a vortex method and confirmed by crossed polarized light microscopy, small-angle X-ray scattering, and rheological measurements. Moreover, the release behaviors and permeation results of PN from the gels were estimated using in vitro studies. Finally, the anti-glaucoma effect of LC gels was evaluated by in vivo animal experiments. The inner structure of the gels was Pn3m-type Q2 and H2 phase, and both of them showed pseudoplastic fluid properties based on characterization techniques. In vitro release profiles suggested that PN could be sustainably released from LC gels within 48 h. Compared with eye drops, Q2 and H2 gel produces a 5.25-fold and 6.23-fold increase in the Papp value (p < .05), respectively, leading to a significant enhancement of corneal penetration. Furthermore, a good biocompatibility and longer residence time on precorneal for LC gels confirmed by in vivo animal experiment. Pharmacokinetic studies showed that LC gels could maintain PN concentration in aqueous humor for at least 12 h after administration and remarkably improve the bioavailability of drug. Additionally, in vivo pharmacodynamics studies indicated that LC gels had a more significant intraocular pressure-lowering and miotic effect compared to eye drops. These research findings hinted that LC gels would be a promising pharmaceutical strategy for ocular application to enhance the efficacy of anti-glaucoma.

Keywords: IOP-lowering; Phytantriol; anti-glaucoma; liquid crystal gels; ocular delivery.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Images of FQ (A) and FH (B) formulations under CPLM (all images were taken at ×100 magnification and the scale bar is 100 μm). SAXS profiles of FQ (C) and FH (D) formulations at 25 ± 0.5 °C, appearance pictures of FQ (a) and FH (b) formulations at room temperature. (E) Schematic illustration of the inner structure of Pn3m-type Q2 and H2 phases containing PN molecules.
Figure 2.
Figure 2.
(A) Flow curves showing the effect of shear rate sweep on viscosity of the LC gels. (B) Rheological profiles of LC gels were evaluated by strain sweep at 0.01–100%. (C) Viscous and elastic moduli dependence upon oscillation frequency for LC gels. (D) The complex viscosity of LC gels at 37 ± 0.5 °C as a function of angular frequency. (E) The cumulative release profiles of PN from different formulations. The inset panel exhibits the drug release flux graph. (F) Ex vivo transcorneal permeation profiles of PN from LC gels and eye drops using fresh rabbit corneas. Data are reported as mean ± SD of n = 3. *p<.05, statistically significant compared with eye drops. **p<.01, compared with eye drops.
Figure 3.
Figure 3.
(A) The lower fornix of the rabbits’ eyes and the anterior surface of the eyeball. (B) Fluorescence photographs of rabbit eyes after application of sodium fluorescein-loaded formulations. Orange and white arrows indicate the release of sodium fluorescein by the gels and the location of the eyeball, respectively.
Figure 4.
Figure 4.
Representative histological images of the eye tissues after treated with various formulations for a week (original magnification, ×200). EP: epithelium; ST: stroma; EN: endothelium; ONL: outer nuclear layer; INL: inner nuclear layer; GCL: ganglion cell layer.
Figure 5.
Figure 5.
PN concentration in rabbits’ aqueous humor at different time points after administration of LC gels and a commercial PN eye drops (all outcomes are reported as mean ± SD of n = 3). *p<.05, statistically significant compared with eye drops. **p<.01, compared with eye drops.
Figure 6.
Figure 6.
(A) Ocular surface was inspected by a slit lamp (a) before establishment of model and (b) after treatment with various formulations. Time-course measurements of (B) pupil diameter and (C) IOP after administration of different PN-loaded formulations in normal rabbits. Time-course measurements of (D) IOP and (E) pupil diameter after administration of different preparations for two weeks in glaucomatous rabbits. *p<.05, statistically significant difference from eye drops. **p<.01, statistically significant compared with eye drops.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Adams CM, Stacy R, Rangaswamy N, et al. (2018). Glaucoma – next generation therapeutics: impossible to possible. Pharm Res 36:25. - PubMed
    1. Almeida H, Amaral MH, Lobão P, et al. (2014). In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov Today 19:400–12. - PubMed
    1. Barauskas J, Landh T (2003). Phase behavior of the phytantriol/water system. Langmuir 19:9562.
    1. Boyd BJ, Whittaker DV, Khoo SM, et al. (2006). Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int J Pharm 309:218–26. - PubMed
    1. Chou SF, Luo LJ, Lai JY (2016). Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers. Acta Biomater 38:116–28. - PubMed

MeSH terms

Grants and funding

The authors gratefully acknowledge the support from the National Natural Science Foundation of China (Nos. 81803831 and 81873019), Anhui Provincial Talents Project for Youth in Universities (No. gxyq2018025), Innovative Entrepreneurship Training Program for College Students of Anhui University of Chinese Medicine (No. 2019011), and Key University Natural Science Research Project of Anhui Province (KJ2018A0301).