Download PDF
Drug Res (Stuttg) 2014; 64(10): 541-547
DOI: 10.1055/s-0033-1363957
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

A Targeting Drug Delivery System for Ovarian Carcinoma: Transferrin Modified Lipid Coated Paclitaxel-loaded Nanoparticles

R. Li
1   Key Laboratory of Food Biotechnology of Sichuan Province, School of Bioengineering, Xihua University, Chengdu, P. R. China
,
Q. Zhang
2   West China School of Pharmacy, Sichuan University, Chengdu, P. R. China
,
X.-y. Wang
2   West China School of Pharmacy, Sichuan University, Chengdu, P. R. China
,
X.-g. Chen
1   Key Laboratory of Food Biotechnology of Sichuan Province, School of Bioengineering, Xihua University, Chengdu, P. R. China
,
Y.-x. He
1   Key Laboratory of Food Biotechnology of Sichuan Province, School of Bioengineering, Xihua University, Chengdu, P. R. China
,
W.-y. Yang
1   Key Laboratory of Food Biotechnology of Sichuan Province, School of Bioengineering, Xihua University, Chengdu, P. R. China
,
X. Yang
1   Key Laboratory of Food Biotechnology of Sichuan Province, School of Bioengineering, Xihua University, Chengdu, P. R. China
› Author Affiliations
Further Information

Publication History

received 21 June 2013

accepted 05 December 2013

Publication Date:
17 January 2014 (online)

Also available at
    Permissions and Reprints

Abstract

The transferring modified lipid coated PLGA nanoparticles, as a targetable vector, were developed for the targeting delivery of anticancer drugs with paclitaxel (PTX) as a model drug to the ovarian carcinoma, which combines the advantages and avoids disadvantages of polymeric nanoparticles and liposomes in drug delivery. A transmission electron microscopy (TEM) confirmed the lipid coating on the polymeric core. Physicochemical characterizations of TFLPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the TFLPs were more efficiently endocytosed by the A2780 cells with high expression of transferrin receptors than HUVEC cells without the transferrin receptors. Furthermore, the anticancer efficacy of TFLPs on the tumor spheroids was stronger than that of lipid coated PLGA nanoparticles (LPs) and PLGA nanoparticles. In the in vivo study, the TFLPs showed the best inhibition effect of the tumor growth for the ovarian carcinoma-bearing mice. In brief, the TFLPs were proved to be an efficient targeting drug delivery system for ovarian carcinoma.

Key words

transferrin modified lipid coated nanoparticles - PLGA - targeting drug delivery system - ovarian carcinoma - paclitaxel
 

  • References

  • 1 Shahzad MK, Shin YH. Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma. Cancer Lett 2012; 18: 76-85
    PubMedGoogle Scholar
  • 2 Chao HT, Wang L. Low dose histone deacetylase inhibitor, LBH589, potentiates anticancer effect of paclitaxel in epithelial ovarian cancer via PI3K/Akt pathway. Cancer Lett 2012; 2: 29-38
    PubMedGoogle Scholar
  • 3 Gould N, Sill MW, Mannel RS et al. A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intra peritoneal carboplatin and intra peritoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2012; 125: 54-58
    CrossrefPubMedGoogle Scholar
  • 4 Despierre E, Lambrechts D. The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. GynecolOncol 2010; 117: 358-365
    PubMedGoogle Scholar
  • 5 Curtin JP, Blessing JA. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a gynecologic oncology group study. J Clin Oncol 2001; 19: 1275-1278
    PubMedGoogle Scholar
  • 6 McGuire WP, Blessing JA. Paclitaxel has moderate activity in squamous cervix cancer. A gynecologic oncology group study. J Clin Oncol 1996; 14: 792-795
    Google Scholar
  • 7 Rose PG, Blessing JA. D.M Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 1999; 17: 2676-2680
    PubMedGoogle Scholar
  • 8 Chua DT, Sham JS. A phase II study of docetaxel and cisplatin as first line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral. Oncol 2005; 41: 589-595
    PubMedGoogle Scholar
  • 9 McCarthy JS, Tannock IF. A phase II trial of docetaxel and cisplatin in patients with recurrent or metastaticnasopharyngeal carcinoma. Oral Oncol 2002; 38: 686-690
    CrossrefPubMedGoogle Scholar
  • 10 Horwitz SB. Taxol (paclitaxel): mechanisms of action. Ann Oncol 1994; 5: 3-6
    CrossrefPubMedGoogle Scholar
  • 11 Liebmann J, Cook JA. Solvent for paclitaxel, and toxicity. Lancet 1993; 342: 14-28
    PubMedGoogle Scholar
  • 12 Sznitowska M, Klunder M, Placzek M. Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin. Chem Pharm Bull 2008; 56: 70-74
    CrossrefPubMedGoogle Scholar
  • 13 Zhang L, Langer RS. Nanoparticles in Medicine: Therapeutic Applications and Developments. Clin Pharmacol Ther 2008; 83: 761-769
    CrossrefPubMedGoogle Scholar
  • 14 Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. NatRev Drug Discov 2005; 4: 145-160
    PubMedGoogle Scholar
  • 15 Zhang L, Zhang L. Lipid polymer hybrid nanoparticles: synthesis, characterization and applications. Nano Life 2010; 1: 163-173
    CrossrefPubMedGoogle Scholar
  • 16 Rossiello R, Carriero MV. Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. J Clin Pathol 1984; 37: 51-55
    CrossrefPubMedGoogle Scholar
  • 17 Shindelman JE, Ortmeyer AE, Sussman HH. Demonstration of the transferrin receptor in human breast cancer tissue. Potential marker for identifying dividing cells. Int J Cancer 1981; 27: 329-334
    CrossrefPubMedGoogle Scholar
  • 18 Jin C, Bai L. Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells. Pharm Res 2009; 26: 1776-1784
    CrossrefPubMedGoogle Scholar
  • 19 Yang XJ, Koh CG. Transferrin Receptor-Targeted Lipid Nanoparticles for Delivery of an Antisense Oligodeoxyribonucleotide against Bcl-2. Mol Pharm 2009; 6: 221-230
    CrossrefPubMedGoogle Scholar
  • 20 Chiu SJ, Liu SJ. Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes. J Controlled Release 2006; 112: 199-207
    CrossrefPubMedGoogle Scholar
  • 21 Du J, Lu WL, Ying X et al. Dual-targeting to potecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood-brain barrier and survival of brain tumor-bearing animals. Mol Pharm 2009; 6: 905-917
    CrossrefPubMedGoogle Scholar
  • 22 Kobayashi H, Man S, Graham CH et al. Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA 1993; 90: 3294-3298
    CrossrefPubMedGoogle Scholar