Ifosfamide-loaded poly (lactic-co-glycolic acid) PLGA-dextran polymeric nanoparticles to improve the antitumor efficacy in Osteosarcoma.
BACKGROUND
Osteosarcoma is a typical bone cancer that primarily affects adolescents. The therapeutic activity of drugs is limited by their severe drug-related toxicities, therefore, a therapeutic approach which is less toxic and highly effective in tumor is of utmost importance.


METHODS
In this study, ifosfamide-loaded poly (lactic-co-glycolic acid) (PLGA)-dextran polymeric nanoparticles (PD/IFS) was developed and studied its anticancer efficacy against multiple osteosarcoma cancer cells. The drug-loaded nanoparticle was characterized for physical and biological characterizations.


RESULTS
The formulated PD/IFS showed a high drug loading capacity and displayed a pH-sensitive release pattern, with a sustained release profile of the IFS. PD/IFS nanoparticles exhibited remarkable in vitro anticancer activity comparable to that of free IFS solution in a concentration dependent manner in MG63 and Saos-2 cancer cells. PLGA-dextran by itself did not affect cell viability of cancer cells indicating its excellent biocompatibility. The formulation exhibited significantly higher PARP and caspase-3/7 expression in both the cancer cells.


CONCLUSIONS
Our study successfully demonstrated that nanoparticulate encapsulation of antitumor agent will increase the therapeutic efficacy and exhibit a greater induction of apoptosis and cell death.
Department of Orthopedic, The First Affiliated Hospital of Medical School of Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310003, China. chenbin501@yeah.net.
Bin
B
Chen
Department of Laboratoire Central, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, 310003, China. yangjz2145@tom.com.
Jie-Zuan
JZ
Yang
Department of Orthopedic, The First Affiliated Hospital of Medical School of Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310003, China. lifengwang122@163.com.
Li-Feng
LF
Wang
Department of Orthopedic, The First Affiliated Hospital of Medical School of Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310003, China. yijun3100@yeah.net.
Yi-Jun
YJ
Zhang
Department of Orthopedic, The First Affiliated Hospital of Medical School of Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310003, China. linxj1900123@gmail.com.
Xiang-Jin
XJ
Lin
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans; D004195:Disease Models, Animal; D004337:Drug Carriers; D065546:Drug Liberation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D019344:Lactic Acid; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology*; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; D003911:Dextrans; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D053148:Caspase 3; D007069:Ifosfamide