September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Penetration of Nanostructured lipid carriers (NLCs) across the Cornea following Topical Administration
Author Affiliations & Notes
  • Sangly P Srinivas
    Indiana University, Bloomington, Indiana, United States
  • P Niamprem
    Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
  • W Chaiyasan
    Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
  • Uday B Kompella
    University of Colorado, Denver, Colorado, United States
  • Waree Tiyaboonchai
    Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
  • Footnotes
    Commercial Relationships   Sangly Srinivas, None; P Niamprem, None; W Chaiyasan, None; Uday Kompella, None; Waree Tiyaboonchai, None
  • Footnotes
    Support  Thailand Research Fund (TRF) under the Royal Golden Jubilee Ph.D. Program to P. Niamprem and W. Tiyaboonchai
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5715. doi:
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      Sangly P Srinivas, P Niamprem, W Chaiyasan, Uday B Kompella, Waree Tiyaboonchai; Penetration of Nanostructured lipid carriers (NLCs) across the Cornea following Topical Administration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5715.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Nanoparticles-based drug/gene delivery have been reported for potential therapeutic management of various ocular surface and corneal disorders. In this study, we have investigated the penetration kinetics of nanostructured lipid carriers (NLCs) across the cornea following topical application at a microscopic scale.

Methods : NR-loaded NLCs (NR-NLCs) were prepared by high-pressure homogenization technique using a mixture of solid lipids and oils (Cetyl palmitate and medium chain Triglyceride). The particle size and surface charge of the NR-NLCs were characterized by ZetaPAL analyzer. The penetration kinetics of NR-NLCs across porcine cornea were assessed by exposure of cornea to NR-NLCs in Ringers and held underneath the objective on a precision for all trans-corneal measurements using a custom-built confocal scanning microfluorometer (CSMF) for 8 h (n=6). CSMF was equipped with a water-immersion objective (Zeiss 40x; 0.75 NA and wd = 1.2 mm). NR fluorescence was excited by an intensity modulated (as a sine wave at 10 kHz) white LED after filtering through an interference filter (565 ± 10 nm). The fluorescence and scattered light from the cornea passing through a parfocal exit slit of the CSMF were detected by two photomultiplier tubes (R928 Hamamatsu) coupled to two independent lock-in amplifiers. The NR in castor oil (NR-CO) and Ringers containing 5%, v/v, DMSO were used to compare the penetration profiles.

Results : NR-NLCs were well dispersed with a particle size of < 50 nm (42 ± 3 nm) and possessed a negative surface charge with a zeta potential of -32 ± 3 mV. NR was not released from NR-NLCs within 8 h, indicating that NR-NLCs could act as tracer of NLCs. Upon 4-8 h exposure of the corneal surface, the NR-NLCs showed significant fluorescence gradients across the epithelium and in the anterior stroma. Moreover, the magnitude of the fluorescence noted upon exposure to NR-NLCs across the epithelium and in the stroma was much greater when compared to that obtained with NR-CO. Profiles similar to those with NR-NLCs were also noted when NR was dissolved in Ringers containing DMSO.

Conclusions : NLCs penetrate the corneal epithelium easily, and possibly even into the hydrophilic stroma. Our results also show that lipophilic solutes penetrate the cornea much better when loaded into NLCs. Therefore, NLCs form a promising carrier for delivery of lipophilic drugs to ocular surface.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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