title: A pH-sensitive binary drug delivery system based on poly(caprolactone)-heparin conjugates.
abstract: PCL-heparin conjugates were synthesized by coupling mono-hydroxyl terminated PCL (Mn = 2000-10000 g/mol) with heparin via EDC/NHS chemistry. The conjugates enabled to self-assemble into the core-shell nanoparticles in around 100 nm diameter to load binary anti-cancer drugs. Lipophilic and neutral paclitaxel (PTX) was first encapsulated in the core, and then hydrophilic and positive charged doxorubicin (DOX) was incorporated into the negative charged shell of PTX loaded nanoparticles via the electrostatic interaction. The in vitro release profiles of the binary-drug loaded nanoparticles revealed that both PTX and DOX were sustainably released from the particles but behaved differently. The release of DOX was pH dependent, ensuring more drug to be released in the tumor cells than in the normal ones. Hence these particles were featured by a sequential controlled drug delivery behavior with a significant cytotoxicity to cervical cancer (Hela cell) and breast cancer (MDA-MB-321) cells. The CLSM observations clearly indicated that both loaded PTX and DOX aggregated in the nucleus of tumor cells to exert their anti-tumor pharmacodynamic effect on the cells.
authors.affiliation: Department of Materials Physics and Chemistry, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Zemin
authors.initials: Z
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xuan
authors.initials: X
authors.lastname: Yin
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Aiying
authors.initials: A
authors.lastname: Zhang
authors.forename: Zengguo
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; D004317:Doxorubicin; D006493:Heparin; D017239:Paclitaxel
keywords: PCL-heparin conjugate; binary-drug delivery system; doxorubicin; pH sensitive; paclitaxel