Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid
tumors. However, significant variability has been detected in their intra-
tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-
tumor accumulation and distribution of weekly sequentially administered
oxaliplatin (l-OHP)-containing PEGylated
liposomes. In that study, the first and second doses of l-OHP-containing PEGylated
liposomes were distributed diversely and broadly within
tumor tissues, resulting in a potent anti-
tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad
liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-
tumor accumulation and distribution of "empty" PEGylated
liposomes. Intra-
tumor distribution of sequentially administered "empty" PEGylated
liposomes was altered in a dosing interval-dependent manner. In addition, the intra-
tumor distribution pattern was closely related to the chronological alteration of
tumor blood flow as well as vascular permeability in the growing
tumor tissue. These results suggest that the sequential administrations of PEGylated
liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within
tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems.