title: Doxorubicin-loaded highly porous large PLGA microparticles as a sustained- release inhalation system for the treatment of metastatic lung cancer.
abstract: Doxorubicin-loaded highly porous large PLGA microparticles (Dox PLGA MPs) were prepared using a w/o/w double emulsification method using ammonium bicarbonate effervescent salt. The prepared Dox PLGA MPs were characterized by particle size analysis, scanning electron microscopy, and confocal microscopy. In vitro cytotoxicity to B16F10 melanoma cells and lung deposition in C57BL/6 mice were examined, and finally the anti-tumor efficacy of pulmonary administered Dox PLGA MPs was evaluated in a mouse model of B16F10 melanoma metastasis. Results showed that Dox PLGA MPs were highly porous, had high encapsulation efficiency, and good aerosolization characteristics. Doxorubicin was gradually released from Dox PLGA MPs over 2 weeks, and after pulmonary administration, Dox PLGA MPs were deposited in lungs and remained in situ for up to 14 days. Furthermore, exposure to Dox PLGA MPs killed B16F10 cells in vitro within 24 h. In particular, tumors in B16F10-implanted mice treated with Dox PLGA MPs were remarkably smaller in terms of mass and number than those in non-treated B16F10-implanted mice. We believe that doxorubicin-loaded highly porous large PLGA microparticles have great potential as a long-term inhalation agent for the treatment of lung cancer.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Republic of Korea.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kim
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Byeon
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules / Q000008:administration & dosage* / Q000138:chemical synthesis; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D002214:Capsules; D003692:Delayed-Action Preparations; D008081:Liposomes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin