In vitro and in vivo investigation of a novel two-phase delivery system of 2-methoxyestradiol liposomes hydrogel.
For improving effectiveness of conventional chemotherapy of subcutaneous tumor, we selected 2-methoxyestradiol (2-ME) as a model drug, local injectable PLGA-PEG-PLGA copolymer thermosensitive hydrogel loading 2-ME liposomes instead of free 2-ME as a novel two-phase drug delivery system was developed, which avoid rapid clearance of liposomes following systemic administration. This new transport system was characterized in vitro and in vivo including rheological behavior, thermo-sensitiveness, stability, released character and intratumoral delivery. The PLGA-PEG-PLGA copolymer solution exhibited still reversible thermosensitive property and better syringeability after incorporated 2-ME liposomes. The 2-ME liposomes were demonstrated stable in the hydrogel by five methods such as scanning electron microscopy (SEM), fluorescent labeling, opalescence, particle size and ultrafiltration methods. Results showed that intact liposomes could be released from the hydrogel and following zero-order model, and sustained release one-two months in vitro and in vivo. In vivo release data demonstrating that 2-ME liposomes could be transported to tumor site, improved therapeutic efficacy and bioavailability of 2-ME liposomes in subcutaneous tumor chemotherapy.
Department of Pharmacy, Children's Hospital of Zhengzhou City , Zhengzhou , China and.
YaBing
Y
Xing
HaiYan
H
Chen
ShuYun
S
Li
XinHong
X
Guo
D000077584:2-Methoxyestradiol; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D012212:Rheology; D013696:Temperature; D013697:Thermosensing
D020100:Hydrogels; D008081:Liposomes; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D004958:Estradiol; D000077584:2-Methoxyestradiol