Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

Abstract

A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.

Fmoc-Conjugated PEG-Vitamin E2 Micelles for Tumor-Targeted Delivery of Paclitaxel: Enhanced Drug-Carrier Interaction and Loading Capacity

“…4, incubation of RBC with PEI caused significant hemolysis in a dose-dependent manner. In contrast, PEG 5K -FVE 2 caused less than 5% hemolysis at both 0.2 and 1 mg/mL, which is considered as nonhemolytic according to the Guiding Principles of Hemolysis Test [H]GPT4-1 (20). These data suggest that the PEG 5K -FVE 2 polymer is hemocompatible and suitable for intravenous administration.…”

Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors

“…43 Many chemotherapeutic agents for cancer, including methotrexate, cisplatin, paclitaxel, docetaxel and doxorubicin, have successfully been formulated in PMs. A few representative studies describing PMs for drug delivery applications of cancer include poloxamer-based micelles, 47 PEG-PLA micelles, 48 PEGylated polyglutamic acid micelles 49 and PEG-PAA micelles. 45 …”

Recent advances in polymeric micelles for anti-cancer drug delivery

“…methotrexate (188) PEG-poly(L-glutamic acid) dichloro(1,2-diaminocyclohexane)platinum (II) (DACHpt) (189) paclitaxel, (190) PEG-poly(L-aspartate) doxorubicin (191) cis-dichlorodiammine platinum (II) (CDDP) (192) Arg-Gly-Asp (RGD) PEG-PLA paclitaxel (193) mPEG-PLA Ethaselen (194) PEG-poly(L-aspartatic acid) adriamycin (195) poly (ethylene oxide)-block-poly (β-benzyl-l-aspartate)(PEO-PBLA) doxorubicin (196) Poly(N-vinylpyrrolidone)-blockpoly(d,l-lactide) paclitaxel (197) docetaxel (197) teniposide (197) etoposide (197) …”