Liposomal Doxorubicin Loaded PLGA-PEG-PLGA for the Treatment of Osteosarcoma
LIANG Guo-hui1, MA Kun1, XIE Yan1, FAN Yong-chun2, ZHAO Cheng-lei2*
1. Luoyang Orthopedic-Traumatological Hospital of Henan Province, Luoyang 471002, China; 2. Jiangsu Province Academy of Traditional Chinese medicine, Nanjing 210028, China
Abstract:OBJECTIVE To prepare the hybrid system of liposomal doxorubicin (DOX-Lip) loaded thermogel (DOX-Lip-Gel) and investigate the in vitro properties and antitumor effect. METHODS Doxorubicin liposomes were prepared by hydration membrane method. Their particle size distribution and entrapment efficiency were investigated. And the in vitro release, viscosity measurement and the anti-tumor efficiency of DOX-Lip-Gel were also investigated. RESULTS The DOX-Lip was prepared with the particle size of (89.3±4.7) nm and the drug entrapment efficiency of (85.3±2.6)%, the liposomes loaded hydrogel was in a sol state at 25 ℃ and converted into the gel state at 37 ℃ with the phase transition temperature of 30 ℃ and could degrade gradually during the time in vivo. The DOX release out of DOX-Lip-Gel could be in a sustained manner up to 200 h with no burst release. An orthotopic osteosarcoma model was adopted and the results revealed that DOX-Lip-Gel had the better antitumor efficiency. CONCLUSION DOX-Lip-Gel could significantly inhibit the growth of osteosarcoma in mice orthotopic model.
LV C, HAO Y, TU G. MicroRNA-21 promotes proliferation, invasion and suppresses apoptosis in human osteosarcoma line MG63 through PTEN/Akt pathway [J]. Tumor Biol, 2016, 37(7):9333-9342.
[2]
LING M, LIU Y, XIA C, et al. Polymer-drug nanoparticles combine doxorubicin carrier and heparin bioactivity functionalities for primary and metastatic cancer treatment.[J]. Mol Pharm, 2017, 14(2):513-522
[3]
ZHANG B, YANG X, WANG Y, et al. Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin hydrochloride[J]. Mater Sci Eng C , 2017, 75:198-206.
[4]
ZHAO D, WU J, LI C, et al. Precise ratiometric loading of PTX and DOX based on redox-sensitive mixed micelles for cancer therapy[J]. Coll Surf B Biointerfaces, 2017, 155:51-60.
[5]
SONIA G, RICCI V, VAVASSORI C, et al. Plasmatic and chamber-specific modulation of cardiac microRNAs in an acute model of DOX-induced cardiotoxicity [J]. Biomed Pharmacother, 2019, 110:1-8.
[6]
CAGEL M, TESAN F C, BERNABEU E, et al. Polymeric mixed micelles as nanomedicines: Achievements and perspectives[J]. Eur J Pharm Biopharm, 2017, 113:211-228.
[7]
WANG H, ZHANG X, LIU Y, et al. Stabilization of liposomes by perfluorinated compounds[J]. ACS Omega, 2018, 3(11):15353-15360.
[8]
GAO Y, SUN Y, REN F, et al. PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.[J]. Drug Dev Ind Pharm, 2010, 36(10):1131-1138.
[9]
WHITE J C, SAFFER E M, BHATIA S R. Alginate/PEO-PPO-PEO composite hydrogels with thermally-active plasticity.[J]. Biomacromolecules, 2013, 14(12):4456-4464.
[10]
ZHANG Z, NI J, CHEN L, et al. Biodegradable and thermoreversible PCLA-PEG-PCLA hydrogel as a barrier for prevention of post-operative adhesion.[J]. Biomaterials, 2011, 32(21):4725-4736.
[11]
LATIF N, BACHHAWAT B K. Liposomes in immunology [J]. J Bio Sci, 1984, 6(4):491-502.
[12]
YANG W, YANG Z, FU J, et al. The influence of trapping agents on the antitumor efficacy of irinotecan liposomes: head-to-head comparison of ammonium sulfate, sulfobutylether-β-cyclodextrin and sucrose octasulfate [J]. Biomater Sci, 2019, 7(1):419-428.
[13]
LIU Y, LIU J. Growing a nucleotide/lanthanide coordination polymer shell on liposomes [J]. Langmuir, 2019, 35(34): 11217-11224.
[14]
DAYAL P, PILLAY V, BABU R J, et al. Box-behnken experimental design in the development of a nasal drug delivery system of model drug hydroxyurea: Characterization of viscosity, in vitro drug release, droplet size, and dynamic surface tension [J]. AAPS PharmSciTech, 2005, 6(4):573-585.
[15]
KHALEDI S, JAFARI S, HAMIDI S, et al. Preparation and characterization of PLGA-PEG-PLGA polymeric nanoparticles for co-delivery of 5-Fluorouracil and Chrysin [J]. J Biomater Sci Polym Ed, 2020,31(5):1-20.
[16]
GAO Y, REN F, DING B, et al. A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel [J]. J Drug Target, 2011, 19(7):516-527.
[17]
KHANNA C, KHAN J, NGUYEN P, et al. Metastasis-associated differences in gene expression in a murine model of osteosarcoma[J]. Cancer Res, 2001, 61(9):3750-3759.
[18]
BURKE T G, MI Z H. The structural basis of camptothecin interactions with human serum albumin-impact on drug stability [J]. J Med Chem, 1994, 37(1): 40-46.
[19]
ZHANG J, GUO Y, PAN G, et al. Injectable drug-conjugated DNA hydrogel for local chemotherapy to prevent tumor recurrence [J]. ACS Appl Mater Interfaces, 2020, 12, 21441-21449.
[20]
HOARE T R, KOHANE D S. Hydrogels in drug delivery: progress and challenges[J]. Polymer, 2008,49:1993-2007.
[21]
ZHANG Y, ZHANG J, XU W, et al. Tumor microenvironment-labile polymer-doxorubicin conjugate thermogel combined with docetaxel for in situ synergistic chemotherapy of hepatoma[J]. Acta Biomater, 2018,77:63-73.