Synthesis, optimization, and characterization of camptothecin-loaded acetalated dextran porous microparticles for pulmonary delivery

Mol Pharm. 2012 Feb 6;9(2):290-8. doi: 10.1021/mp2003785. Epub 2012 Jan 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals / chemistry
  • Administration, Inhalation
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Camptothecin / administration & dosage*
  • Camptothecin / chemistry
  • Cell Line, Tumor
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry*
  • Dextrans / chemistry*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid / chemistry
  • Lung*
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / metabolism
  • Microspheres
  • Molecular Weight
  • Particle Size
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Porosity

Substances

  • Acetals
  • Antineoplastic Agents, Phytogenic
  • Delayed-Action Preparations
  • Dextrans
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Camptothecin