Biomedical subjects

G W Tin

Publications and source records attributed to G W Tin.

7 recordsLinked to original sources

PubMed1985

Biodistribution of phospholipid vesicles in mice bearing Lewis lung carcinoma and granuloma.

Murine biodistributions of vesicle-encapsulated [111In]NTA were obtained under a number of conditions. These included normal animals, those bearing s.c.- or i.v.-implanted Lewis Lung Carcinoma (LLC) and those having both s.c.-LLC and sterile granuloma. Variations in the distributions were observed with a preinjection of unlabeled aminomannose (AM) vesicles or an increase in the labeled vesicle size. It was found that s.c. LLC exhibited uptake of between 10 and 25% injected dose/g (% ID/g) depending upon tumor mass with larger lesions having lower accumulation. Significant uptake enhancement (p less than 0.05) occurred after AM blockade. Similar results hold for the i.v.-injected LLC cells implying targeting to both primary and metastatic sites. By increasing vesicle size by a factor of 4, uptake by s.c. LLC declined to essentially blood levels; e.g., 2% ID/g. Granuloma accumulations were also at circulating values and, unlike s.c. LLC, could not be imaged.

Animals↗

PubMed1983

Liposomal blockade of the reticuloendothelial system: improved tumor imaging with small unilamellar vesicles.

The reticuloendothelial system of mice bearing EMT6 tumors was effectively blocked by intravenous injections of small unilamellar vesicles that incorporated a 6-aminomannose derivative of cholesterol in the lipid bilayer. Neutral liposomes loaded with indium-111-nitrilotriacetic acid were then injected. Fifty percent more radioactivity was deposited in tumors of the animals with blocked reticuloendothelial systems than in controls. Twenty-four hours after the injection of radioactive vesicles, well-defined tumor images were observed in whole-body gamma camera scintigraphs. Biodistribution studies showed that tumors from animals with blocked reticuloendothelial systems had more than twice the radioactivity per gram than any other tissue analyzed.

Animals↗

PubMed1983

Stability of erythrocyte ghosts: a gamma-ray perturbed angular correlation study.

The structural integrity of erythrocyte ghosts made by the preswell and slow-dialysis techniques has been studied in vitro by use of gamma-ray perturbed angular correlation (PAC) techniques and also by standard in vitro leakage methods employing sequestered labeled markers. Complexes of 111In3+ and nitrilotriacetate were encapsulated in ghosts made from human, rabbit, rat, and mouse erythrocytes, and their leakage was monitored by both methods. In addition, 125I-labeled bovine serum albumin was encapsulated, and ghost integrity was monitored by conventional leakage measurements. With the PAC technique the percentage of material released from human ghosts was determined quantitatively, and the results were equivalent to those obtained by the conventional method. In addition, at various times after intravenous injection, tissue distribution of the ghosts in the mouse was studied. The percent injected dose per gram of tissue of the labeled surface proteins of erythrocyte ghosts in circulation approximated that of the entrapped labeled albumin. This suggests that the ghost membrane and contents are strongly associated in vivo. Large 125I-labeled bovine serum albumin molecules and small 111In3+-nitrilotriacetate complexes were delivered in high quantitites to the lung initially, and to the liver and spleen. Because erythrocyte ghosts have the ability to entrap a wide range of substances and deliver them to specific organs, ghosts may be preferable to other drug carriers or drug therapy for treatment of certain disorders.

Animals↗

PubMed1983

Tumor-imaging potential of liposomes loaded with In-111-NTA: biodistribution in mice.

EMT6 tumors in BALB/c mice have been successfully imaged with small (less than 0.1 mu), unilamellar lipid vesicles (SUVs) loaded with In-111 nitrilotriacetic acid (In-111 NTA). Neutral SUVs prepared from distearoyl phosphatidylcholine (DSPC) and cholesterol (CH) (ratio 2:1) delivered sufficient radioactivity to allow tumor visualization 24 hr after i.v. injection; so did positively and negatively charged SUVs with the ratio 4:1:1 for DSPC:CH:X, were X was stearylamine or dicetyl phosphate. Other SUVs containing a 6-aminomannose or 6-aminomannitol derivative of cholesterol did not cause significant tumor accumulation of In-111 NTA, and tumor images were not readily discernible. The maximum tumor-associated radioactivity, 18.5% of injected dose per gram of tissue, was achieved with neutral SUVs. This level of tumor-associated In-111 was over 4 times that observed when unencapsulated In-111 NTA was injected. Neutral SUVs also gave the lowest specific activities in the liver and spleen (14.6% and 18.8% of dose respectively).

Acetates↗

PubMed1982

Stability of carbohydrate-modified vesicles in vivo: comparative effects of ceramide and cholesterol glycoconjugates.

The stability and tissue distribution of lipid vesicles modified at the surface by the incorporation of either a galactosyl ceramide (GalCer) or a galactosyl cholesterol (GalChol) glycoconjugate have been studied in mice by measuring the release of vesicle-entrapped 111In. Although the tissue distributions of both vesicle types were similar, the GalCer-containing vesicles were markedly less stable than those prepared with GalChol, whether administered orally or by intraperitoneal injection. Physical characterization of the vesicles in vitro suggests that the increased disruption rate for GalCer vesicles in vivo is related to structural instabilities induced by the cerebroside, which can then result in either an increased rate of vesicle uptake by tissues or a greater susceptibility to lysis. These studies demonstrate the importance of the nonpolar anchoring groups in determining the fate of surface-modified vesicles in vivo.

Administration, Oral↗

PubMed1981

Effect of surface modification on aggregation of phospholipid vesicles.

Phospholipid vesicles have been extensively investigated because of their usefulness as models for biological membranes and their potential application as carriers for drug delivery. However, preparations of small sonicated vesicles tend to aggregate and fuse (on storage at room temperature and at 4 degrees C), resulting in significant changes in turbidity, rate of uptake by macrophage, and proton NMR linewidths. By modification of the surface of phospholipid vesicles with charged groups such as beta-aminogalactose that extend significantly from the vesicle surface, it is possible to obtain preparations that are stable for greater than 7 days.

Animals↗

PubMed1981

Phagocytosis of carbohydrate-modified phospholipid vesicles by macrophage.

Modification of the surface of distearoyl phosphatidylcholine vesicles with synthetic glycolipids dramatically affects the rate of uptake of these vesicles by mouse peritoneal macrophage. The high rate of uptake of 6-aminomannose-modified vesicles is effectively inhibited by cytochalasin B and chloroquine but not by colchicine, indicating that the mechanisms of vesicle uptake is phagocytosis. Other modified vesicles appear to have some effect on the rate of uptake of 6-aminomannose-modified vesicles suggesting that the various vesicle types compete for the same initial binding sites. Analysis of 6-aminomannose-modified vesicles by gamma-ray perturbed angular correlation spectroscopy shows that the rotational correlation time of the encapsulated 111In3+ does not change when the vesicles associate with macrophage. This result is consistent with transmission electron microscopy, which indicates that the aminomannose-modified vesicles remain intact after phagocytosis as aggregates of fused and intact vesicles surrounded by a single bilayer membrane structure.

Animals↗