title: Synergistic anti-glioma effect of a coloaded nano-drug delivery system.
abstract: The anti-glioma effect of temozolomide (Tem) is sometimes undermined by the emerging resistance. Recently, resveratrol (Res), herbal medicine extracted from grape seeds, has been demonstrated for its potential use in chemosensitization. In the current study, both these drugs were loaded simultaneously into nanoparticles with methoxy poly(ethylene glycol)-poly epsilon caprolactone (mPEG-PCL) as drug carriers in order to achieve better antitumor efficiency. Tem/Res-coloaded mPEG-PCL nanoparticles were constructed, characterized, and tested for antitumor effect on glioma cells by using in vitro and xenograft model system. The nanoparticle constructs were satisfactory with drug loading content (Res =~12.4%; Tem =~9.3%) and encapsulation capacity of >85% for both the drugs. In addition, the coencapsulation led to better in vitro stability of the nanoparticles than Tem-loaded nanoparticles. An in vitro uptake study demonstrated a high uptake efficiency of the nanoparticles by glioma cells. The synergistic antitumor effect against glioma cells was observed in the combinational treatment of Res and Tem. Tem/Res-coloaded nanoparticles induced higher apoptosis in U87 glioma cells as compared to cells treated by the combination of free drugs. Tem/Res-coloaded particles caused more effective inhibition of phosphor-Akt, leading to upregulation of the downstream apoptotic proteins. In addition, the in vivo study showed the superior tumor delaying effect of coloaded nanoparticles than that of free drug combination. These results suggest that Tem/Res-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for glioma therapy.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing.
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Yancheng City No 1 People's Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jia
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Pankaj Kumar
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng.
authors.forename: Shu
authors.initials: S
authors.lastname: Ruan
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004337:Drug Carriers; D004338:Drug Combinations; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D004338:Drug Combinations; D011091:Polyesters; D013267:Stilbenes; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D003606:Dacarbazine; D000077185:Resveratrol; D000077204:Temozolomide
keywords: drug delivery; mPEG-PCL; polymeric; resveratrol; synergy; temozolomide