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

• Published in: Journal of controlled release 2012-10, Vol.163 (2), p.130-135
• Main Authors: Xu, Qingxing, Xia, Yujie, Wang, Chi-Hwa, Pack, Daniel W.
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemistry; Biological and medical sciences; Chitosan; Chitosan - chemistry; DNA - chemistry; Double-walled microspheres; Doxorubicin; Doxorubicin - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; drug therapy; encapsulation; Gene therapy; General pharmacology; genes; Genetic Therapy; lactic acid; Lactic Acid - chemistry; Medical sciences; Microspheres; molecular weight; nanoparticles; Nanoparticles - chemistry; p53; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids; PLGA; Polyglycolic Acid - chemistry; Tumor Suppressor Protein p53 - genetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.08.032

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 75μm and uniform shell thickness of 8 to 17μm. 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. [Display omitted]