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Pegylated Liposomes Have Potential as Vehicles for Intratumoral and Subcutaneous Drug Delivery

Imperial Cancer Research Fund Oncology Unit, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0HS, United Kingdom [K. J. H., G. R-B., K. N. S.]; Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55902 [K. J. H., R. G. V.]; Sequus Pharmaceuticals Inc., Menlo Park, California 94025 [P. S. U.]; and Department of Radiotherapy, Charing Cross Hospital, London W6 8RP, United Kingdom [J. S. W. S.]

The potential value of intratumoral or s.c. injections of pegylated liposomes as locoregionally targeted therapy of tumors and their draining lymph nodes was assessed in nude mice as part of an ongoing program aimed at developing pegylated liposomal radiosensitizers for the treatment of head and neck cancers. Animals received ¹¹¹In-labeled diethylenetriaminepentaacetic acid (DTPA), either encapsulated in pegylated liposomes (IDLPL) or in the unencapsulated form (¹¹¹In-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 retained 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 ¹¹¹In-DTPA was 204.4%ID/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 ¹¹¹In-DTPA showed no evidence 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 24,051.1%ID/g·h. Unencapsulated ¹¹¹In-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:contralateral 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 ¹¹¹In-DTPA in the draining nodes. Locoregional administration of pegylated liposomal radiosensitizers may be a useful approach for targeted therapy of head and neck tumors and their nodal metastases.

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