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Cisplatin–alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
5927 448 2014 13 PDF Available
Title
Cisplatin–alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells
Abstract

Systemic side effects and low aqueous solubility have limited the clinical use of cisplatin (CDDP) in ovarian carcinoma and have contributed to failures in developing effective drug delivery systems. In order to develop a novel drug delivery system with enhanced efficacy and minimal adverse effects, we exploited the properties of sodium alginate (SA) to synthesize CDDP–SA conjugate (CS), which is highly soluble and readily incorporated into liposomes (CS-PEG-Lip). Epidermal growth factor receptor (EGFR) is overexpressed in many ovarian cancers, therefore we modified EGF on the liposomes (CS-EGF-Lip) to specifically target EGFR-expressing tumors, thereby increasing the bioavailability and efficacy of CDDP. In vitro experiments confirmed that EGF-Lip selectively recognized EGFR-positive SKOV3 cells and effectively penetrated tumor spheroids. We demonstrated that CS-EGF-Lip possessed satisfactory size distribution and exhibited significantly improved encapsulation and loading efficiency. Furthermore, CS-EGF-Lip sustained release of CDDP in vitro, suggesting that CS-EGF-Lip may retain the antitumor activity of CDDP. Inhibition of proliferation and migration was also greater with CS-EGF-Lip compared to CDDP. In vivo xenograft experiments revealed that administration of CS-EGF-Lip enhanced delivery of CDDP into ovarian tumor tissues and improved the antitumor efficacy of CDDP, while reducing nephrotoxicity and body weight loss in mice. These results suggest that CS-EGF-Lip may offer a promising strategy for CDDP delivery in the treatment of EGFR-positive ovarian carcinoma or similar tumors, with enhanced efficacy and fewer adverse effects.

Keywords
Liposome; Cisplatin; Sodium alginate; Ovarian cancer; Epidermal growth factor; Specific drug delivery
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Cisplatin–alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 14, May 2014, Pages 4297–4309
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us