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Changes in Cisplatin Delivery Due to Surface-Coated Poly (Lactic Acid)–Poly(-Caprolactone)Microspheres

Departments of Cardiology, University of Minnesota, Mayo Mail Code: 508, 420 Delaware St. SE, Minneapolis, MN, 55455, USAchand025{at}tc.umn.edu

Robert F. Wilson

Departments of Cardiology, University of Minnesota, Mayo Mail Code: 508, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

Gundu H. R. Rao

Lab Medicine Pathology, University of Minnesota, Mayo Mail Code: 508, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

Gladwin S. Das

Departments of Cardiology, University of Minnesota, Mayo Mail Code: 508, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

Smooth muscle cell proliferation plays a major role in the genesisof restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses, have the potential to prevent restenosis. However, the development of injectable microspheres for sustained drug delivery to the arterial wall is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, cisplatin, in a series of surface coated biodegradable microspheres composed of poly(lactic acid)– poly(caprolactone) blends, with a mean diameter of 2–10 mm. The microspheres were surface coated with poly ethylene glycol (PEG), chitosan (Chit), or alginate (Alg). A solution of cisplatin and a 50: 50 blend of polylactic acid (PLA)– polycaprolactone (PCL) dissolved in acetone–dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol or Chit or Alg) with stirring using a high speedhomogenizer, for the formation of microspheres. Cisplatin recovery inmicrospheres ranged from 25–45% depending on the emulsification system used for the preparations. Scanning electron microscopy revealed that the PLA–PCL microspheres were spherical in shape and had a smooth surface texture. The amount of drug release was much higher initially (20–30%), this was followed by a constant slow-release profile for a 30-day period of study. It has been found that drugrelease depends on the amount of entrapped drug, on the presence of extra cisplatin in the dispensing phase, and on the polymer coatings.This PEG or Alg-coated PLA/PCL microsphere formulation may have potential for the targeted delivery of antiproliferative agents to treat restenosis.

Key Words: microspheres • cisplatin encapsulation • poly(lactic acid) • poly(-caprolactone) • poly(ethylene glycol) • chitosan • alginate • controlled release

Journal of Biomaterials Applications, Vol. 16, No. 4, 275-291 (2002)
DOI: 10.1106/088532802024246


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