title: Synthesis, optimization, and characterization of camptothecin-loaded acetalated dextran porous microparticles for pulmonary delivery.
abstract: We propose the use of a new biopolymer, acetalated dextran (Ac-DEX), to synthesize porous microparticles for pulmonary drug delivery. Ac-DEX is derived from the polysaccharide dextran and, unlike polyesters, has tunable degradation from days to months and pH neutral degradation products. Ac-DEX microparticles fabricated through emulsion techniques were optimized using a variety of postprocessing techniques to enhance the respirable fraction for pulmonary delivery. Tangential flow filtration resulted in a maximum 37% respirable fraction for Ac-DEX porous microparticles, compared to a 10% respirable fraction for poly(lactic-co-glycolic acid) (PLGA) porous microparticles. Ac-DEX microparticles were of an optimum diameter to minimize macrophage clearance but had a low enough theoretical density for deep lung penetration. Transepithelial electrical resistance (TEER) measurements showed that the particles did not impinge on a monolayer of lung epithelial cells in either air or liquid conditions. Also, the release of the chemotherapeutic camptothecin was shown to be tunable depending on Ac-DEX degradation time and molecular weight, and drug release was shown to be bioactive over a range of concentrations. Our results indicate that both release kinetics and fraction of burst release of drug from Ac-DEX porous microparticles can be tuned by simply changing the Ac-DEX polymer properties, affording a large range of formulation options for drug delivery to the pulmonary cavity. Overall, Ac-DEX porous microparticles show promise as an emerging carrier for pulmonary delivery of drugs to the alveolar region of the lung, particularly for the treatment of lung diseases.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Meenach
authors.forename: Yu Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kauffman
authors.forename: Naveen
authors.initials: N
authors.lastname: Kanthamneni
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D000080:Acetals / Q000737:chemistry; D000280:Administration, Inhalation; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D008168:Lung; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity
chemical_list: D000080:Acetals; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D003911:Dextrans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002166:Camptothecin