The objective of the proposed research is the characterization of the multiple pathways of the uptake and degradation of liposomes in the liver at the cellular level. The program is geared to apply the method of centrifugal elutriation for fractionating liver cells, the technique of gamma ray perturbed angular correlation, and other bioanalytical methods for investigating the influence of the dose of liposomal lipid and other properties of liposomes on various pathways of uptake and degradation of liposomes and their entrapped contents in the liver. The focus is on studying various approaches of regulating the pathways of uptake and degradation of liposomes in tissue culture systems, in the system of a perfused liver, and in rats and mice in vivo.
The specific aims of the proposed research program are directed toward the following two main areas: (1) to investigate how the delivery of liposomes and their content to the lysosomal and the cytoplasmic compartment of the parenchymal cells, and to the endothelial and Kupffer cells are regulated by the presence of terminated-galactose glycolipids and lipophilic insulin derivatives in liposomes under various formulating and dosing conditions. (2) to study how the rate and extent of release of liposomal content are regulated by where and how the liposomes are degraded at various cellular sites of uptake.
|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|
|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|
|Chen, F; Liu, Y; Lu, J et al. (1992) A sensitive fluorometric assay for reducing sugars. Life Sci 50:651-9|
|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