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Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.

Publication ,  Journal Article
Ramakumar, S; Phull, H; Purves, T; Funk, J; Copeland, D; Ulreich, JB; Lai, L-W; Lien, Y-HH
Published in: J Urol
September 2005

PURPOSE: Ischemia/reperfusion injury is a leading cause of renal damage and antisense gene therapy has been shown to ameliorate its effects. However, this approach has been limited by current delivery methods that require high concentrations of intravenous nucleic acids lacking specificity for targeting tissues. To overcome these limitations we developed a novel murine partial nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant as a topical oligonucleotide delivery system. MATERIALS AND METHODS: A total of 18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion. Hydrogel primer and then sealant were applied to the cut surface and photopolymerized. Using this method 16 additional mice received hydrogel primer mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 microg). Kidneys were harvested at various time points and assessed for oligonucleotide penetration using fluorescence microscopy. RESULTS: A survival rate of 100% (34 subjects) was obtained using this mouse model of partial nephrectomy. PEG hydrogel provided adequate protection against renal hematoma and intraperitoneal blood. Fluorescent images revealed that 50 microg was the minimum dose resulting in complete progressive cellular penetration with time. In addition to direct diffusion from the application site, movement of oligonucleotide through the subcapsular space into the cortex was an observed mechanism of distribution. CONCLUSIONS: A murine partial nephrectomy model was successfully created using PEG hydrogel. In addition to achieving hemostasis, hydrogel served as a successful depot for delivering oligonucleotides throughout the kidney.

Duke Scholars

Published In

J Urol

DOI

ISSN

0022-5347

Publication Date

September 2005

Volume

174

Issue

3

Start / End Page

1133 / 1136

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Tissue Distribution
  • Reperfusion Injury
  • Oligonucleotides
  • Nephrectomy
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Mice, Inbred C57BL
  • Mice
  • Kidney Cortex
 

Citation

APA
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MLA
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Ramakumar, S., Phull, H., Purves, T., Funk, J., Copeland, D., Ulreich, J. B., … Lien, Y.-H. (2005). Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model. J Urol, 174(3), 1133–1136. https://doi.org/10.1097/01.ju.0000168617.17080.46
Ramakumar, Sanjay, Hardeep Phull, Todd Purves, Joel Funk, Duan Copeland, Judith B. Ulreich, Li-Wen Lai, and Yeong-Hau Howard Lien. “Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.J Urol 174, no. 3 (September 2005): 1133–36. https://doi.org/10.1097/01.ju.0000168617.17080.46.
Ramakumar S, Phull H, Purves T, Funk J, Copeland D, Ulreich JB, et al. Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model. J Urol. 2005 Sep;174(3):1133–6.
Ramakumar, Sanjay, et al. “Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.J Urol, vol. 174, no. 3, Sept. 2005, pp. 1133–36. Pubmed, doi:10.1097/01.ju.0000168617.17080.46.
Ramakumar S, Phull H, Purves T, Funk J, Copeland D, Ulreich JB, Lai L-W, Lien Y-HH. Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model. J Urol. 2005 Sep;174(3):1133–1136.
Journal cover image

Published In

J Urol

DOI

ISSN

0022-5347

Publication Date

September 2005

Volume

174

Issue

3

Start / End Page

1133 / 1136

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Tissue Distribution
  • Reperfusion Injury
  • Oligonucleotides
  • Nephrectomy
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Mice, Inbred C57BL
  • Mice
  • Kidney Cortex