title: Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy.
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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois, 600 S. Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Qingxing
authors.initials: Q
authors.lastname: Xu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Xia
authors.forename: Chi-Hwa
authors.initials: CH
authors.lastname: Wang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Pack
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D016159:Tumor Suppressor Protein p53; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D004247:DNA; D048271:Chitosan