The American Journal of Surgery
Volume 198, Issue 6 , Pages 781-786, December 2009

A novel intralymphatic nanocarrier delivery system for cisplatin therapy in breast cancer with improved tumor efficacy and lower systemic toxicity in vivo

  • Mark S. Cohen, M.D., F.A.C.S.

      Affiliations

    • Department of Surgery, University of Kansas, Medical Center, Kansas City, KS, United States
    • SC and MSC are co-first authors.
    • ,
  • Shuang Cai, M.S.

      Affiliations

    • Department of Pharmaceutical Chemistry, 2095 Constant Ave., University of Kansas, Lawrence, KS 66047, United States
    • SC and MSC are co-first authors.
    • ,
  • Yumei Xie, Ph.D.

      Affiliations

    • Department of Pharmaceutical Chemistry, 2095 Constant Ave., University of Kansas, Lawrence, KS 66047, United States
    • ,
  • M. Laird Forrest, Ph.D.

      Affiliations

    • Department of Pharmaceutical Chemistry, 2095 Constant Ave., University of Kansas, Lawrence, KS 66047, United States
    • Corresponding Author InformationCorresponding author. Tel.: +1-785-864-4388; fax: +1-785-864-5736

Received 5 March 2009; received in revised form 2 June 2009

Abstract 

Background

A lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity.

Methods

Human breast cancer cells (107 MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm3, intravenous cisplatin or subcutaneous hyaluronan-cisplatin (HA-cisplatin) nanoconjugate was given 1/week × 3 weeks at 3.3 mg/kg (platinum basis).

Results

Nanoconjugates colocalized with the tumors after subcutaneous peritumoral injection and showed improved efficacy to intravenous cisplatin. After 1 month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared with subcutaneous HA-cisplatin nanoconjugates.

Conclusions

This nanocarrier delivery platform focuses on delivering drugs to the areas in which tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC.

Keywords: Lymphatic chemotherapy, Nanoconjugate, Cisplatin, Localized chemotherapy

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 Supported in part by grants from NIH (R21 CA132033-01, P20 RR015563) and the American Cancer Society (RSG-08-133-01-CDD).

PII: S0002-9610(09)00554-6

doi:10.1016/j.amjsurg.2009.07.032

The American Journal of Surgery
Volume 198, Issue 6 , Pages 781-786, December 2009

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