Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency

Zongrui Zhang; Xinyu Wang; Binbin Li; Yuanjing Hou; Zhengwei Cai; Jing Yang; Yi Li

doi:10.1039/c7ra12683b

Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency

RSC Adv. 2018 Jan 16;8(6):3274-3285. doi: 10.1039/c7ra12683b. eCollection 2018 Jan 12.

Authors

Zongrui Zhang^{1

2}, Xinyu Wang^{1

2}, Binbin Li^{1

2}, Yuanjing Hou^{1

2}, Zhengwei Cai^{1

2}, Jing Yang³, Yi Li⁴

Affiliations

¹ State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology Wuhan 430070 China wangxinyu@whut.edu.cn +86-27-87880734 +86-27-87651853.
² Biomedical Materials and Engineering Research Center of Hubei Province Wuhan 430070 China.
³ School of Foreign Languages, Wuhan University of Technology Wuhan 430070 China.
⁴ Institute of Textiles and Clothing, The Hong Kong Polytechnic University Hung Hom Kowloon Hong Kong P. R. China.

Abstract

The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened in vitro anti-hepatoma efficiency than that of free PTX and smooth MS. The in vivo studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.