Antitumor Effects of Hydroxycamptothecin-Loaded Poly[ethylene glycol]-poly[-benzyl-L-glutamate] Micelles Against Oral Squamous Cell Carcinoma

Authors: Ding, Xue-Qiang1; Chen, Dan1; Wang, An-Xun1; Li, Su2; Chen, Yu1; Wang, Ji1

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 16, Number 7, July 2006 , pp. 313-323(11)

Publisher: Cognizant Communication Corporation

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Abstract:

Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is limited by its poor solubility and rapid destruction. Amphiphilic block copolymer micelle carriers possess significant potential for improving drug solubility and stability. Poly[ethylene glycol]-poly[-benzyl-L-glutamate] (PEG-PBLG) micelles were prepared and loaded with the active lactone form of HCPT using an uncomplicated dialysis method. HPLC and scanning electron microscopy studies revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active, open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy techniques. The golden hamster cheek pouch squamous cell carcinoma model was employed for in vivo studies; encapsulated lactone and open ring-carboxylated forms of HCPT were administered intraperitoneally, followed by determinations of tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the open ring-carboxylated and encapsulated drugs displayed comparable in vitro cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT lactone produced greater and more prolonged tumor suppression compared to the open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles against oral squamous cell carcinoma in vivo are concluded to be superior to those exerted by open ring-carboxylated HCPT.

Keywords: Amphiphilic block copolymer micelles; Hydroxycamptothecin (HCPT); Oral squamous cell carcinoma (OSCC); Poly[ethylene glycol] (PEG); Poly[-benzyl-L-glutamate] (PBLG); Poorly soluble drugs

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000006783980991

Affiliations: 1: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou City, Guangdong Province, 510080, P.R. China 2: Skate Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou City, Guangdong Province, 510080, P.R. China

Publication date: July 1, 2006

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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