May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
High-Efficacy Site-Directed Drug Delivery System Using Sialyl-lewis X Conjugated Liposome
Author Affiliations & Notes
  • N. Hashida
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • N. Ohguro
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • Y. Tano
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • N. Yamazaki
    Advanced Industrial Science and Technology, Tsukuba, Japan
  • Footnotes
    Commercial Relationships  N. Hashida, None; N. Ohguro, None; Y. Tano, None; N. Yamazaki, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3182. doi:
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      N. Hashida, N. Ohguro, Y. Tano, N. Yamazaki; High-Efficacy Site-Directed Drug Delivery System Using Sialyl-lewis X Conjugated Liposome. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3182. doi:

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

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Purpose: : A novel type of liposomal nanoparticle was developed that conveys sialyl-Lewis X (sLeX) on the liposomal membrane to achieve accurate and efficient binding to the cognate E-selectin, P-selectin, or both (ARVO 2007). The aim of this study was to evaluate the new developed sialyl-Lewis X conjugated liposome (sLeXL) as a site-directed delivery system to activated endothelial cells in vivo using murine experimental autoimmune uveoretinitis (EAU) model.

Methods: : Two types of nanoparticles were prepared: sLeXL-containing dexamethasone (d-sLeXL, total dexamethasone 2 µg/100 µL d-sLeXL solution) and sLeXL containing Cy5.5 (sLeXL-C). The controls for these substances, respectively, were liposomes without a sugar chain: liposome without sLeX containing dexamethasone (d-L) and liposome without sLeXL containing Cy5.5 (L-C). To estimate the equivalent dose of systemic free dexamethasone, cluster analysis of the expression pattern of selected genes was carried out in inflamed eyes in the mice that received d-sLeXL and those given free dexamethasone (0.04, 0.2, 0.4, 0.6, 0.8, 1.0, and 2.0 mg per mouse, respectively). To evaluate the systemic distribution, sLeXL-C or L-C was injected into the tail vein of mice (50 µl/mouse). Using eXplore Optix (GE Healthcare Co., Ltd., Tokyo Japan), a fluorescent signal of Cy5.5 was monitored every 5 minutes (up to 30 minutes) in the entire body of the mouse. To determine the behavior of liposome, transmission electron microscopy (TEM) of the eye injected with sLeXL-C was carried out. Eyeballs from EAU mice not injected with sLeXL-C served as controls.

Results: : Hierarchical cluster analysis showed that the d-sLeXL group and the 1-mg group formed a cluster and highlighted that the sLeXL solution containing 2-µg dexamethasone regulated the inflammation genes in the inflamed tissue the same way as the 1-mg dexamethasone solution. Both sLeXL-C and L-C accumulated primarily in the liver. The fluorescence associated with tissue absorbance increased in a time-dependent manner and lasted up to 24 hours during observation. The ultratructure of the choriocapillaris in EAU mice injected with sLeXL discriminated the presence of a great number of particles that was undetected in specimens from the control group. The size of these particles was comparable to that of sLeXLmeasured in vitro.

Conclusions: : sLeXL can be a highly efficacious site-directed system in vivo. Using sLeXL as a vehicle for drug delivery, substantial pharmacologic effects with minimum side effects in inflammatory diseases should be achieved.

Keywords: uveitis-clinical/animal model • drug toxicity/drug effects • microscopy: electron microscopy 

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