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Abstract

Tumor cells often metastasize through lymphatic channels. It follows that localization of antitumor agents in the lymphatics may be therapeutically beneficial. This study determines the extent to which lipid composition controls lymphatic transport of a model compound ((14)C-sucrose) in liposomes following intraperitoneal administration in rats. All liposomes tested had mean diameters of approximately 0.2 µm. Liposomes were administerd to thoracic duct cannulated rats, and (14)C was quantified in thoracic lymph, several lymph nodes, blood, urine, and peritoneal wash. Changing liposome composition altered the rate of absorption of (14)C from the peritoneal cavity, stability in biological fluids, and the relative ability of liposomes to be retained by lymph nodes. Stability in biological fluids (plasma and lymph) appeared to be a reasonable predictor of observed lymph node recovery. Direct measures of lymph node level alone were poor measures of the ability of liposomes to function as prototypal lymphatic drug carriers. Neutral liposomes were better at reaching the general circulation following absorption from the peritoneal cavity.

Effect of the Poly(ethylene glycol) (PEG) Density on the Access and Uptake of Particles by Antigen-Presenting Cells (APCs) after Subcutaneous Administration

“…6–19 The latter strategy is more practical and simple for mass vaccination as it does not require specialized techniques of injections. Several design parameters that affect the trafficking and accumulation of synthetic vaccines (e.g., liposomes or nanoparticles) in lymphoid organs have been studied, such as particle size, 6–8 surface chemistry (charge, 9,10,20 hydrophobicity 11–15 ), and cell-targeting moieties (e.g., antibody 10 ).…”

Antitumoral Activity of Liposomes and Immunoliposomes Containing 5-Fluorouridine Prodrugs

“…Lip- osomes are probably retained in the peritoneum for long periods due to the obstruction of lymphatic drainage occurring in many carcinomas. 52,53 Monoclonal antibodies covalently linked to the liposome surface may confer greater tumor specificity within the peritoneal cavity. 45,54 Intraperitoneal administration of liposomes or immunoliposomes should avoid two major problems that limit the usefulness of the intravenously injected liposomes/immunoliposomes, i.e.…”

“…15 This process to same extent is circumvented in an ip-disseminated carcinomatosis by the partial obstruction of the lymphatics by the tumor mass, which leads to an effective antitumor activity of liposomes. [52][53][54]61 Finally, if the therapeutic efficacy depends on the diffusion of free drugs released from the cell-bound immunoliposomes or liposomes, through the cell membrane, the choice of a lipophilic prodrug would be important, because only a hydrophobic drug can more readily penetrate lipophilic barriers. After encapsulation within liposomes or immunoliposomes, the drug is much more strongly retained in the tumor tissue, thus avoiding systemic toxicity.…”

A critical period requiring Rho proteins for cell cycle progression uncovered by reversible protein transduction in endothelial cells

“…The BAECs were cultured as described [21]. The cells were plated at a confluent density of 25% and the progression of the S phase of the cell cycle was evaluated by propidium iodide staining as previously described [22].…”