title: Inhalable microspheres embedding chitosan-coated PLGA nanoparticles for 2-methoxyestradiol.
abstract: Developing a highly effective and lung-targeted local drug delivery carrier with low irritancy may be critical for improving treatment of lung cancer. Using soluble excipients as microspheres (MS) matrix, respirable MS embedding chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (CNP-MS) for 2-methoxyestradiol (2-ME) were designed, which could avoid macrophage phagocytosis to achieve the targeted delivery of these drugs. 2-ME CNP-MS were prepared by spray-drying and characterized by morphology, redispersability, fine particle fraction (FPF) and drug release. Cytotoxicity, and lung deposition and histological examination were investigated. Results showed that 2-ME CNP-MS were spherical with a rough surfaces, exhibiting good redispersability, a high respirable fraction and sustained release characteristics. CNP-MS markedly enhanced the cytotoxicity of 2-ME by approximately 8.8-fold and 3.65-fold on SPC-A1 cells compared to solution and NP, respectively. After pulmonary administration, 2-ME CNP were distributed in rat lungs and for 10 mg of 2-ME CNP-MS, haematoxylin and eosin staining showed no obvious difference compared to the untreated control group. Therefore, CNP-MS revealed suitable features for local lung delivery and significantly enhanced cytotoxicity of 2-ME without obvious inflammation in lungs of rats, suggesting that 2-ME CNP-MS have great potential as an inhalation agent for targeted, highly effective and safe treatment of lung cancer.
authors.affiliation: School of Pharmacy, Zhengzhou University , Zhengzhou , People's Republic of China.
authors.forename: XinHong
authors.initials: X
authors.lastname: Guo
authors.forename: XinXin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: YongWei
authors.initials: Y
authors.lastname: Hao
authors.forename: YaLin
authors.initials: Y
authors.lastname: Zhao
authors.forename: ZhenZhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000077584:2-Methoxyestradiol; D000280:Administration, Inhalation; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004958:Estradiol; D000077584:2-Methoxyestradiol; D048271:Chitosan
keywords: Cytotoxicity; fine particle fraction; in vivo; inflammation; local lung delivery; spray-drying