International Journal of Nanomedicine (Oct 2019)
Fabrication Of Dual pH/redox-Responsive Lipid-Polymer Hybrid Nanoparticles For Anticancer Drug Delivery And Controlled Release
Abstract
Wanfu Men,1 Peiyao Zhu,1 Siyuan Dong,1 Wenke Liu,1 Kun Zhou,1 Yu Bai,1 Xiangli Liu,1 Shulei Gong,1 Can Yang Zhang,2 Shuguang Zhang1 1Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210, USACorrespondence: Shuguang ZhangDepartment of Thoracic Surgery, The First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, People’s Republic of ChinaTel +86 13909886618Email [email protected] Yang ZhangSingapore-MIT Alliance for Research and Technology, 1 Create Way, #03-12/13/14 Enterprise Wing, Singapore 138602, SingaporeTel +65 9499 0710Email [email protected]: The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance.Methods: In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pKb value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility.Results: The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX.Conclusion: All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.Keywords: pH-sensitive, redox-sensitive, lipid-polymer, hybrid, drug delivery, anticancer, stimuli-responsiveness
