Polylactide-graft-doxorubicin nanoparticles with precisely controlled drug loading for pH-triggered drug delivery

Yun Yu, Chih Kuang Chen, Wing Cheung Law, Emily Weinheimer, Sanghamitra Sengupta, Paras N. Prasad, Chong Cheng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

114 Citations (Scopus)


Nanoparticles (NPs) with high drug loading and pH-responsivity were prepared by nanoprecipitation of a hydrophobic polymer-drug conjugate (PDC). The PDC, polylactide-graf t-doxorubicin (PLA-g-DOX), was synthesized by azide-alkyne click reaction to transform acetylenefunctionalized PLA into PLA-graf t-aldehyde (PLA-g-ALD), followed by DOX conjugation to form acid-sensitive Schiff base linkage between drug moieties and polymer scaffold. The DOX loading amount in PLA-g-DOX PDC was determined to be 32 wt % by1H NMR and UV-vis spectroscopies. PLA-g-DOX PDC was further used to prepare NPs with precisely controlled drug loading by nanoprecipitation in the presence of a PEGylated surfactant. The effects of organic solvent, PLA-g-DOX PDC concentration and PLA-g-DOX/surfactant mass ratio on size and size distribution of NPs were systematically examined based on analysis by dynamic light scattering (DLS) and transmission electron microscopy (TEM). NPs prepared under the optimal conditions exhibited well-defined spherical morphology with volume-average hydrodynamic diameter (Dh) around 100 nm. Due to the Schiff base conjugation linkage in PLA-g-DOX PDC, acid-sensitive drug release behavior of the NPs was observed. In vitro studies against MCF-7 breast cancer cells showed that the NPs can be readily taken up and result in enhanced therapeutic efficiency as compared to DOX·HCl, indicating their promising potential applications as anticancer nanomedicines.
Original languageEnglish
Pages (from-to)524-532
Number of pages9
Issue number2
Publication statusPublished - 10 Feb 2014

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


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