Abstract

The objective of the proposed research is to characterize the multiple pathways of the cellular uptake and the subsequent degradation of liposomes in the liver. The program is geared to utilize the technique of gamma ray perturbed angular correlation, the approach of liver perfusion, and other analytical methods to investigate the influence of liposome dose and liposome properties on the extent and the rate of cellular uptake and degradation of liposomes in the liver of a mouse. The focus is on studying various pathways which control the uptake and degradation of liposomes in the liver. The goal of the proposed research program will encompass the following specific aims: (1) To test the hypothesis that the rate and extent of release of liposome contents in the liver depend upon accessibility of liposomes to various cellular sites of degradation, namely, the nonlysosomal, extracellular degradation and the intrecellular degradation in Kupffer cells, endothelial cells, and parenchymal cells, respectively. (2) To study the influence of liposome dose and liposome properties on the potential multiple pathways of the celllular uptake and degradation of liposomes in the liver.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK034013-02
Application #
3232403
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1984-07-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Pharmacy
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Morimoto, K; Yamahara, H; Lee, V H et al. (1994) Transport of thyrotropin-releasing hormone across rat alveolar epithelial cell monolayers. Life Sci 54:2083-92
Yamahara, H; Morimoto, K; Lee, V H et al. (1994) Effects of protease inhibitors on vasopressin transport across rat alveolar epithelial cell monolayers. Pharm Res 11:1617-22
Ma, W; Hwang, K J; Lee, V H (1993) A fluorescence quenching method for estimating chelating groups in chelate-conjugated macromolecules. Pharm Res 10:204-7
Narawane, M; Podder, S K; Bundgaard, H et al. (1993) Segmental differences in drug permeability, esterase activity and ketone reductase activity in the albino rabbit intestine. J Drug Target 1:29-39
Lehr, C M; Lee, V H (1993) Binding and transport of some bioadhesive plant lectins across Caco-2 cell monolayers. Pharm Res 10:1796-9
Ma, W; Hwang, K J; Lee, V H (1993) Use of the gamma-ray perturbed angular correlation (PAC) technique for monitoring liposomal phospholipid bilayer integrity. Pharm Res 10:252-7
Chen, F; Liu, Y; Lu, J et al. (1992) A sensitive fluorometric assay for reducing sugars. Life Sci 50:651-9
Yamamoto, A; Hayakawa, E; Kato, Y et al. (1992) A mechanistic study on enhancement of rectal permeability to insulin in the albino rabbit. J Pharmacol Exp Ther 263:25-31
Chow, D D; Essien, H E; Padki, M M et al. (1989) Targeting small unilamellar liposomes to hepatic parenchymal cells by dose effect. J Pharmacol Exp Ther 248:506-13
Essien, H; Lai, J Y; Hwang, K J (1988) Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes. J Med Chem 31:898-901

Showing the most recent 10 out of 12 publications