Microencapsulation of Poorly Water-soluble Finasteride in Polyvinyl Alcohol/chitosan Microspheres as a Long-term Sustained Release System for Potential Embolization Applications

Xiaohong Li,1

Kun Chen,1

Xiongfa Ji,2

Xi Yuan,3

Zehua Lei,3

Muhammad Wajid Ullah,1,*,Email

Jun Xiao3,*,Email

Guang Yang1,*,Email

1Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

2Department of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

3Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Abstract

Prostatic artery embolization (PAE) has been widely applied as an alternative option to treat symptomatic benign prostatic hyperplasia (BPH). However, hitherto, very few drug-loaded embolic materials have been developed to improve the therapeutic efficacy of PAE. In this study, the poorly water-soluble finasteride (FNS) was micronized via a homogenization technique in the presence of a hydrophilic surfactant, followed by encapsulating the crystalline FNS dispersion in polyvinyl alcohol/chitosan (PVA/CS) matrix via emulsification crosslinking method. The prepared FNS-loaded PVA/CS microspheres ([email protected]/CS MS) were characterized for their physicochemical properties. Results showed that the MS were well-dispersed and spherical, with an average particle size of 191.5 μm. The FNS was presented in crystalline form inside the MS, which exhibited controlled and sustained release of FNS up to 45 days. In vitro biocompatibility evaluations indicated that the MS were non-cytotoxic and hemocompatible. Moreover, in vivo transauricular embolization studies in rabbits revealed the effective occlusion of the MS in the auricular central arteries, and exhibited superior embolization effects. Furthermore, the persistent embolization resulted in prominent ultrastructural alternations of endothelial cells in ischemic necrosis region. These results suggest that the drug-delivering MS could be a promising embolic agent for BPH therapy.

Microencapsulation of Poorly Water-soluble Finasteride in Polyvinyl Alcohol/chitosan Microspheres as a Long-term Sustained Release System for Potential Embolization Applications