Novel polyion complex micelles for liver-targeted delivery of diammonium glycyrrhizinate: in vitro and in vivo characterization.

Polyion complex micelles (PIC micelles) based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-Chitosan) and lactose-conjugated PEG-grafted-chitosan (Lac-PEG-g-Chitosan) were designed as carriers for anionic drugs. Diammonium glycyrrhizinate (DG)-loaded conventional PIC micelles (mPIC micelles) and lactose-modified PIC micelles (Lac-PIC micelles) were prepared successfully with encapsulation efficiency of 97.4% and 96.7%, respectively. These micelles were uniform spherical particles with a mean size of 21.6 and 26.4 nm by transmission electron microscopy, respectively. No significant size change of these micelles in three months indicated their good physical stability. The in vitro drug release behavior of mPIC micelles in different media as well as the changes of size and zeta potential demonstrated that the drug was released mainly through swelling and diffusion induced by ion exchange. The pharmacokinetic experiments showed that the area under the curve of DG plasma concentration-time profile in rats for mPIC micelles and Lac-PIC micelles were 1.2 times and 0.4 times higher than that for DG injection, respectively. The liver targeting ability of both mPIC micelles and Lac-PIC micelles was evaluated in rats, revealing that Lac-PIC micelles could deliver more DG to liver than mPIC micelles. Therefore, the Lac-PIC micelles prepared in this study were promising liver-targeted nanocarriers for DG.

Amphotericin B-loaded poly(ethylene glycol)-poly(lactide) micelles: preparation, freeze-drying, and in vitro release.

Polymeric micelles prepared from a series of poly(ethylene glycol)-poly(lactide) (PEG-PLA) diblock copolymers with various PLA chain lengths were designed as drug carriers for water insoluble drug amphotericin B (AmB). Physicochemical properties of AmB-loaded micelles were evaluated. Micelles were freeze-dried to obtain long-time stable formulations. The redispersibility of the freeze-dried samples was poor when the weight ratio of PLA block was bigger than the PEG block of the copolymer. Various types of lyoprotectants including saccharides and PEGs with different molecular weight were tested to improve the redispersion performance of the freeze-dried samples. PEG was proved to be more effective than saccharides on stabilizing the micelles during lyophilization when the weight ratio of PLA block was bigger than PEG block. The sustained release in vitro of AmB was evidenced. About 80% of AmB was released in 80 h. The in vitro release behavior could be best described by the first-order equation. The release rate was reduced as enhancing PLA chain length due to the stronger interaction between poorly water-soluble AmB and longer hydrophobic chain length of PLA.