Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery

The potential value of intratumoral or s.c. injections of pegylated liposom es as locoregionally targeted therapy of tumors and their draining lymph no des was assessed in nude mice as part of an ongoing program aimed at develo ping pegylated liposomal radiosensitizers for the treatment of head and nec k cancers, Animals received In-111-labeled diethylenetriaminepentaacetic ad d (DTPA), either encapsulated in pegylated liposomes (IDLPL) or in the unen capsulated form (In-111-DTPA), as intratumoral or s.c. Injections, and the local retention, locoregional nodal drainage, and systemic biodistribution were measured. After intratumoral injections, IDLPL were effectively retain ed in the tumor with an area under the curve (AUC) between 1 and 96 h of 2, 574.4% injected dose per gram hours (%ID/g.h). The corresponding value for In-111-DTPA was 204.4%D/g.h. Accumulation of IDLPL was seen in ipsilateral lymph nodes. The maximal ipsilateral:contralateral node ratios were 8:1 (2. 2 versus 0.27%ID/g) for inguinal nodes at 24 h and 19:1 (2.5 versus 0.13%ID /g) for axillary nodes at 48 h, Unencapsulated In-111-DTPA showed no eviden ce of accumulation in locoregional nodes. After s.c. injection, IDLPL were cleared slowly from the injection site with an AUC between 1 and 192 h of 2 4,051.1%ID/g.h. Unencapsulated In-111-DTPA was cleared rapidly with an AUC between 1 and 192 h of 46.4%ID/g.h. Again, significant levels of IDLPL were detected in the ipsilateral locoregional nodes, with ipsilateral: contrala teral ratios of 121:1 (57.9 versus 0.48%ID/g) at 24 h (inguinal nodes) and 17:1 (5.2 versus 0.3%ID/g) at 72 h (axillary nodes). There was no retention of unencapsulated In-111-DTPA in the draining nodes. Locoregional administ ration of pegylated liposomal radiosensitizers may be a useful approach for targeted therapy of head and neck tumors and their nodal metastases.