Intralymphatic chemotherapy using a hyaluronan-cisplatin conjugate.

The Journal of Surgical Research
Shuang CaiM Laird Forrest


Breast cancers typically spread to regional lymph nodes once they disseminate from the primary tumor, thus adequate evaluation and treatment of the axillary lymph nodes is paramount in early stage disease. One significant problem with current therapy is the side effects chemotherapy agents create systemically, either alone or in combination. The purpose of this study is to determine whether lymphatically targeted cisplatin carriers will increase the localized dose in lymphatic metastases without systemic toxicities. Hyaluronan (HA) is a highly biocompatible polymer that follows lymphatic drainage from the interstitial spaces. We formed complexes of HA and cisplatin by non-covalent conjugation. Complexes were injected subcutaneously into the upper mammary fat pad of female rats, and the tissue distribution determined. Cisplatin-HA contained up to 0.25 w/w of Pt and released drug with a half-life of 10 h in saline. Cisplatin-HA conjugates had high anti-tumor activity in vitro similar to the free drug: cisplatin-HA IC50 7 microg/mL in MCF7 and MDA-MB-231 human breast cancer cells (free cisplatin IC50 7 microg/mL). Cisplatin-HA conjugates were well tolerated in rodents with no signs of injection site morbidity or major organ toxici...Continue Reading


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