Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy

Qingxing Xu, Yujie Xia, Chi Hwa Wang, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

We have designed and evaluated a dual anticancer delivery system to provide combined gene therapy and chemotherapy. Double-walled microspheres consisting of a poly(d,l-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid) (PLA) shell were fabricated via the precision particle fabrication (PPF) technique. We make use of the advantages of double-walled microspheres to deliver chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases, respectively. Different molecular weights of PLA were used to form the shell layer for each formulation. The microspheres were monodisperse with a mean diameter of 65 to 75 μm and uniform shell thickness of 8 to 17 μm. Blank and Dox-loaded microspheres typically exhibited a smooth surface with relatively few small pores, while chi-microspheres containing p53 nanoparticles, with and without Dox, presented rough and porous surfaces. The encapsulation efficiency of Dox was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53 nanoparticles, on the other hand, was not affected by the presence of Dox. As desired, chi-p53 nanoparticles were released first, followed by simultaneous release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have demonstrated that the PPF method is capable of producing double-walled microspheres and encapsulating dual agents for combined modality treatment, such as gene therapy and chemotherapy.

Original languageEnglish
Pages (from-to)130-135
Number of pages6
JournalJournal of Controlled Release
Volume163
Issue number2
DOIs
StatePublished - Oct 28 2012

Bibliographical note

Funding Information:
The authors acknowledge the funding support from the National Institutes of Health (NIH, USA) and National Medical Research Council (NMRC, Singapore) under the grant numbers 1R01EB005181 and NMRC EDG11may084 , respectively. Qingxing Xu acknowledges the scholarship support from Agency for Science, Technology and Research (A*STAR, Singapore) for NUS-UIUC Joint Ph.D. Program.

Keywords

  • Chitosan
  • Double-walled microspheres
  • Doxorubicin
  • Gene therapy
  • PLGA
  • p53

ASJC Scopus subject areas

  • Pharmaceutical Science

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