Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles: barriers from in vitro to in vivo.
نویسندگان
چکیده
A rational development of an efficient siRNA delivery system is important for streamlining the RNAi-based drug development process. However, a huge gap frequently exists between in vitro and in vivo activity, which is the rate-limiting step for developing versatile nanoparticles. We report herein on a remarkable non-linearity in pharmacokinetics (PK), but not pharmacodynamics (PD) using octaarginine (R8) modified lipid nanoparticles in mice. A quantitative study of siRNA molecules between cultured cells and mouse liver revealed a high correlation between intracellular siRNA molecules and their RNAi activities, indicating that there was no significant difference in the efficiency in PD. In contrast, a remarkable difference was observed in the non-linearity in PK. Quantitative analysis of the time profile for siRNA showed that the percentage of siRNA accumulation in mice was severely decreased with decreasing input dose compared to in vitro data. These unexpected data reveal an important clue to bridging the gap between in vitro and in vivo activity.
منابع مشابه
Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles : Barriers from in vitro to in vivo Authors:
متن کامل
Preparation, properties and preclinical pharmacokinetics of low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle
Low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle (LMWH-ISL-SLN) was developed for injective application. The morphological observation, particle diameter and zeta potential of LMWH-ISL-SLN were characterized using transmission electron microscopy (TEM) and a Malvern Zetasizer. Its entrapment efficiency (EE) and drug loading (DL) were determined by ultracen...
متن کاملIn-vitro – In-vivo Characterization of Glimepiride Lipid Nanoparticulates Prepared by Combined Approach of Precipitation and Complexation
Novel lipid nanoparticulates (NCs) were developed by a combined approach of precipitation and complexation with an aim to improve the solubility, stability and targeting efficiency of glimepiride (GLP). GLP NCs were prepared by precipitation process using PEG 20000 and further complexed with phospholipon90G (P90G). The NCs were evaluated for physicochemical characterization, such as drug lo...
متن کاملPreparation, properties and preclinical pharmacokinetics of low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle
Low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle (LMWH-ISL-SLN) was developed for injective application. The morphological observation, particle diameter and zeta potential of LMWH-ISL-SLN were characterized using transmission electron microscopy (TEM) and a Malvern Zetasizer. Its entrapment efficiency (EE) and drug loading (DL) were determined by ultracen...
متن کاملPharmacokinetics and Pharmacodynamics of Gliclazide from Immediate and Modified Release Formulation Tablets in Rats
The objective of the study was to compare pharmacokinetic and pharmacodynamic parameters of gliclazide after administration of immediate (IR) and modified release (MR) tablets. The experiment included rats with both normoglyceamia and streptozocin (STZ)-induced hyperglyceamia. Several MR formulations were designed and in vitro drug release profile was assessed by a dissolution test. For the fur...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of controlled release : official journal of the Controlled Release Society
دوره 161 3 شماره
صفحات -
تاریخ انتشار 2012