Drug Design, Development and Therapy (Mar 2016)
Amsacrine analog-loaded solid lipid nanoparticle to resolve insolubility for injection delivery: characterization and pharmacokinetics
Abstract
Yi-Ping Fang,1 Chih-Hung Chuang,2 Pao-Chu Wu,1 Yaw-Bin Huang,1 Cherng-Chyi Tzeng,3 Yeh-Long Chen,3 Ya-Ting Liu,1 Yi-Hung Tsai,1 Ming-Jun Tsai4–6 1School of Pharmacy, College of Pharmacy, 2Department of Biomedical and Environment Biology, College of Life Science, 3School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, 4Department of Neurology, China Medical University Hospital, 5School of Medicine, Medical College, China Medical University, Taichung, 6Department of Neurology, China Medical University An-Nan Hospital, Tainan, Taiwan Abstract: Amsacrine analog is a novel chemotherapeutic agent that provides potentially broad antitumor activity when compared to traditional amsacrine. However, the major limitation of amsacrine analog is that it is highly lipophilic, making it nonconductive to intravenous administration. The aim of this study was to utilize solid lipid nanoparticles (SLN) to resolve the delivery problem and to investigate the biodistribution of amsacrine analog-loaded SLN. Physicochemical characterizations of SLN, including particle size, zeta potential, entrapment efficiency, and stability, were evaluated. In vitro release behavior was also measured by the dialysis method. In vivo pharmacokinetics and biodistribution behavior of amsacrine analog were investigated and incorporated with a non invasion in vivo imaging system to confirm the localization of SLN. The results showed that amsacrine analog-loaded SLN was 36.7 nm in particle size, 0.37 in polydispersity index, and 34.5±0.047 mV in zeta potential. More than 99% of amsacrine analog was successfully entrapped in the SLN. There were no significant differences in the physicochemical properties after storage at room temperature (25°C) for 1 month. Amsacrine analog-loaded SLN maintained good stability. An in vitro release study showed that amsacrine analog-loaded SLN sustained a release pattern and followed the zero equation. An in vivo pharmacokinetics study showed that amsacrine analog was rapidly distributed from the central compartment to the tissue compartments after intravenous delivery of amsacrine analog-loaded SLN. The biodistribution behavior demonstrated that amsacrine analog mainly accumulated in the lungs. Noninvasion in vivo imaging system images also confirmed that the drug distribution was predominantly localized in the lungs when IR-780-loaded SLN was used. Keywords: amsacrine analog, solid lipid nanoparticle, pharmacokinetics, biodistribution, water insolubility
