Intraperitoneal (IP)
chemotherapy confers significant survival benefits in
cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky
tumors, have prohibited it from becoming a standard of care. We have developed
drug-loaded, polymeric
tumor-penetrating microparticles (TPM) to address these problems. Initial studies showed that TPM provides
tumor-selective delivery and is effective against ovarian SKOV3
tumors of relatively small size (<50 mg). The present study evaluated whether the TPM activity extends to other
tumor types that are more bulky and have different morphologies and disease presentation. We evaluated TPM in mice bearing two IP human pancreatic
tumors with different growth characteristics and morphologies (rapidly growing, large and porous Hs766T vs. slowly growing, smaller and densely packed MiaPaCa2), and at different disease stage (early stage with smaller
tumors vs. late stage with larger
tumors plus
peritoneal carcinomatosis). Comparison of treatments with TPM or
paclitaxel in
Cremophor micelles, at equi-toxic doses, shows, in all
tumor types: (a) higher
paclitaxel levels in
tumors (up to 55-fold) for TPM, (b) greater efficacy for TPM, including significantly longer survival and higher cure rate, and (c) a single dose of TPM was equally efficacious as multiple doses of
paclitaxel/
Cremophor. The results indicate
tumor targeting property and superior antitumor activity of
paclitaxel-loaded TPM are generalizable to small and large peritoneal
tumors, with or without accompanying
carcinomatosis.