alexa Effect of particle size and charge on the disposition of lipid carriers after intratumoral injection into tissue-isolated tumors.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Nomura T, Koreeda N, Yamashita F, Takakura Y, Hashida M

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Abstract PURPOSE: Pharmacokinetic properties of various lipid carriers (liposome and emulsions) after intratumoral injection were studied in perfusion experiments using tissue-isolated tumor preparations of Walker 256 carcinosarcoma. METHODS: Four types of lipid carriers, large emulsion (254 nm), small emulsion (85 nm), neutral liposomes (120 nm) and cationic liposomes (125 nm) were prepared. We quantified their recovery from the tumor, leakage from the tumor surface and venous outflow after intratumoral injection into perfused tissue-isolated tumors, and analyzed venous appearance curves based on a pharmacokinetic model. RESULTS: In contrast to the small emulsion and neutral liposomes, which immediately appeared in the venous outflow perfusate following intratumoral injection, the appearance of the cationic liposomes and the large emulsion was highly restricted, clearly demonstrating that intratumoral clearance of these formulations can be greatly retarded by the cationic charge and large particle size, respectively. The venous appearance rate-time profiles were fitted to equations derived from a two-compartment model by nonlinear regression analysis. When the calculated parameters were compared among these four formulations, the venous appearance rate did not exhibit such a large difference; however, the rate of transfer from the injected site to the compartment which involves clearance by venous outflow was all very different. CONCLUSIONS: The results of this study indicate that the determining factor which alters the pharmacokinetic properties of these lipid carriers after intratumoral injection is not the rate of transfer from the interstitial space to the vascular side but the rate of intratumoral transfer from the injection site to the well-vascularized region.
This article was published in Pharm Res and referenced in Pharmaceutica Analytica Acta

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