TY - JOUR
T1 - Changes in cisplatin delivery due to surface-coated poly (lactic acid)-poly(ε-caprolactone) microspheres
AU - Chandy, Thomas
AU - Wilson, Robert F.
AU - Rao, Gundu H.R.
AU - Das, Gladwin S.
PY - 2002/4
Y1 - 2002/4
N2 - Smooth muscle cell proliferation plays a major role in the genesis of 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 μm. 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 speed homogenizer, for the formation of microspheres. Cisplatin recovery in microspheres 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 drug release 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.
AB - Smooth muscle cell proliferation plays a major role in the genesis of 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 μm. 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 speed homogenizer, for the formation of microspheres. Cisplatin recovery in microspheres 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 drug release 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.
KW - Alginate
KW - Chitosan
KW - Cisplatin encapsulation
KW - Controlled release
KW - Microspheres
KW - Poly(ethylene glycol)
KW - Poly(lactic acid)
KW - Poly(ε-caprolactone)
UR - http://www.scopus.com/inward/record.url?scp=0036525575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036525575&partnerID=8YFLogxK
U2 - 10.1106/088532802024246
DO - 10.1106/088532802024246
M3 - Article
C2 - 12099508
AN - SCOPUS:0036525575
SN - 0885-3282
VL - 16
SP - 275
EP - 291
JO - Journal of Biomaterials Applications
JF - Journal of Biomaterials Applications
IS - 4
ER -