Efficacy of a novel LyP-1-containing self-microemulsifying drug delivery system (SMEDDS) for active targeting to breast cancer


TİMUR S. S., YÖYEN ERMİŞ D., ESENDAĞLI G., YONAT İŞGÜDER S., Horzum U., ESENDAĞLI G., ...More

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol.136, pp.138-146, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 136
  • Publication Date: 2019
  • Doi Number: 10.1016/j.ejpb.2019.01.017
  • Journal Name: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.138-146
  • Keywords: Breast cancer, LyP-1, p32, SMEDDS, Lymphatic targeting, Chemotherapy, SPONTANEOUS EMULSIFICATION, LYMPHATIC-SYSTEM, HOMING PEPTIDE, ORAL BIOAVAILABILITY, TUMOR LYMPHATICS, IN-VIVO, PACLITAXEL, LYP-1, FORMULATION, CELL
  • Lokman Hekim University Affiliated: No

Abstract

An ideal cancer therapy targets the tumor cells selectively without damaging healthy tissues. Even though the tumor-specific markers are limited, these molecules can be used for the delivery of anti-cancer drugs as an active targeting strategy. Since the lymphatic system plays a critical role in the dissemination of cancer cells, the drugs directed through lymphatics can feasibly reach to the sites of metastasis. LyP-1 is a peptide that binds to the p32 receptor which is highly expressed not only on the lymphatic endothelium but also on the malignant cells; thus, making this peptide ligand a preferable candidate to mediate active targeting of lymphatics and cancer cells. In this study, different formulations of LyP-1 containing lipid-based nanophannaceutics so-called self-microemulsifying drug delivery systems (SMEDDS) were developed and tested for their efficacy in targeting breast cancer. Following the selection of non-toxic formulation, doxorubicin hydrochloride and LyP-1 were co-administered in the SMEDDS, which resulted in a significant increase in in vitro cytotoxicity in p32-expressing breast cancer cells, 4T1 and MDA-MB-231. Accordingly, the uptake of LyP-1 in the SMEDDS by the cancer cells was demonstrated. The expression of p32 was detected in the 4T1 tumor tissues which were efficiently targeted with LyP-1 in the SMEDDS. When doxorubicin was co-administrated with LyP-1 in SMEDDS via intraperitonial administration, tumor growth and metastasis were significantly reduced. In conclusion, a novel and efficacious SMEDDS formulation containing LyP-1 with a droplet size less than 100 nm was developed for the lymphatic targeting of breast cancer.