Core-shell nanocarriers with high paclitaxel loading for passive and active targeting.
Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to αVβ3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Improved in vitro and in vivo tumor targeting and penetration were observed with NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD enhanced the accumulation and penetration of NCs in tumors. The NCs were cytocompatible, histocompatible, and non-toxic to other healthy tissues. The endocytosis of NCs was mediated by lipid rafts in an energy-dependent manner, leading to better cytotoxicity of PTX against cancer cells. In contrast with commercial product, PTX-loaded NCs (PTX-NCs) increased area under concentration-time curve (AUC) by about 4-fold, prolonged mean resident time (MRT) by more than 8-fold and reduced the elimination rate constant by greater than 68-fold. In conclusion, the present nanocarriers with high drug-loading capacity represent an efficient tumor-targeting drug delivery system with promising potential for cancer therapy.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Zhu
Z
Jin
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Yaqi
Y
Lv
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Hui
H
Cao
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Jing
J
Yao
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Jianping
J
Zhou
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Wei
W
He
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.
Lifang
L
Yin
D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004705:Endocytosis; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry*; D050997:Nanomedicine / Q000379:methods; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D012995:Solubility
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D008055:Lipids; D053769:Nanocapsules; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel