Synthesis, optimization, and characterization of camptothecin-loaded acetalated dextran porous microparticles for pulmonary delivery.
Summary of "Synthesis, optimization, and characterization of camptothecin-loaded acetalated dextran porous microparticles for pulmonary delivery."
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.
Division of Pharmaceutics, College of Pharmacy and ‡Department of Chemical and Biomolecular Engineering, The Ohio State University , Columbus, Ohio 43210, United States.
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Name: Molecular pharmaceutics
Medical and Biotech [MESH] Definitions
An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Used as a support for ion-exchange chromatography.
The genetic constitution of the individual; the characterization of the genes.
Use of a device (film badge) for measuring exposure of individuals to radiation. It is usually made of metal, plastic, or paper and loaded with one or more pieces of x-ray film.
A plant genus of the family NYSSACEAE (sometimes classified in the CORNACEAE family). It is a source of CAMPTOTHECIN.
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