Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility.
Poly(epsilon-caprolactone) microspheres containing bupivacaine were prepared by the spray-drying process. The average size of drug loaded microspheres was less than 3 microm in diameter, and the percentage of entrapment efficiency was 91 +/- 3%. In vitro drug release kinetic in phosphate buffer at 37 degrees C showed a hyperbolic profile, with a burst-effect during the first hour. Subcutaneous injection of bupivacaine-loaded microspheres in the back of rats caused an increase in drug concentration in plasma. Maximum bupivacaine concentration in plasma was 237 +/- 58 ng/ml at 105 h, and drug was detected in plasma for 16 days. The half-life time of the drug was increased by more than 125 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 30 days of injection, a mass formed by microspheres surrounded by a thin fibrous capsule was observed. Small blood vessels and multinucleate foreign body giant cells with macrophagic function around microspheres were detected. After 60 days of injection a subcutaneous mass was also observed, which was formed of more degraded dispersed microspheres in conjunctive tissue, which had a normal structure. Thus, bupivacaine-loaded poly(epsilon-caprolactone) microspheres could be considered as a device to be used in the treatment of severe pain that is not responsive to opioids for example in cancer-related syndromes or in intractable herpetic neuralgia.
Blanco
M D
MD
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
Bernardo
M V
MV
Sastre
R L
RL
Olmo
R
R
Muñiz
E
E
Teijón
J M
JM
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002021:Buffers; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D002021:Buffers; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; C016240:polycaprolactone; D002045:Bupivacaine