In vitro and in vivo evaluation of APRPG-modified angiogenic vessel targeting micelles for anticancer therapy

• Published in: International journal of pharmaceutics Vol. 486; no. 1-2; pp. 356 - 366
• Main Authors: Guo, Pan, Song, Shuangshuang, Li, Zhao, Tian, Ye, Zheng, Jiatong, Yang, Xinggang, Pan, Weisan
• Format: Journal Article
• Language: English
• Published: Netherlands 30.05.2015
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biological Transport; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; Drug Delivery Systems; Drug Liberation; Humans; Male; Mice; Micelles; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic - drug therapy; Oligopeptides - administration & dosage; Oligopeptides - chemistry; Oligopeptides - pharmacokinetics; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Polyethylene Glycols - chemistry; Polyglactin 910 - chemistry; Tissue Distribution; Tumor Burden - drug effects; Micelle; Long circulation; Anticancer therapy; Tumor targeting; Paclitaxel; Angiogenic vessel targeting
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.03.067

The study was aimed to evaluate the antitumor potential of the Ala-Pro-Arg-Pro-Gly (APRPG)-modified angiogenic vessel targeting drug delivery system using paclitaxel (PTX) as a model drug. In this study, an angiogenesis homing peptide APRPG was conjugated to the amphipathic copolymer PLGA-PEG and the synthesized copolymer APRPG-PEG-PLGA was used to prepare PTX encapsulated micelles (APRPG-PEG-Mic). The micelles were uniform spherical and exhibited a unimodal particle size distribution and a slight negative zeta-potential. The in vitro drug release result demonstrated a significant sustained release property of APRPG-PEG-Mic. Compared to Taxol(®) and Cont-PEG-Mic, APRPG-PEG-Mic showed a stronger cytotoxicity against two cancerous cell lines. In the cell uptake studies, the APRPG-modified micelles enhanced intracellular fluorescent intensity in EA.hy926 cells. The biodistribution study revealed the accumulation of APRPG-PEG-Mic in tumor tissues as a result of passive accumulation and active targeting. In comparison with Taxol(®) and Cont-PEG-Mic, APRPG-PEG-Mic reduced the tumor volume more significantly and prolonged the survival time of tumor-bearing mice, indicating a higher antitumor efficacy and lower systematic side effects of APRPG-PEG-Mic. The results indicated that APRPG-modified micelles could be an efficient target-delivery method to angiogenic vessels and a highly promising therapeutic system in anticancer therapy.