Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.
Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.
Masters
D B
DB
Department of Anesthesia, John Enders Pediatric Research Facility, Children's Hospital, Boston, Massachusetts 02115.
Berde
C B
CB
Dutta
S
S
Turek
T
T
Langer
R
R
D000704:Analysis of Variance; D000818:Animals; D002021:Buffers; D002045:Bupivacaine / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003992:Dibucaine / Q000008:administration & dosage*; D004337:Drug Carriers; D004343:Drug Implants; D066298:In Vitro Techniques; D008297:Male; D009407:Nerve Block; D011091:Polyesters; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013056:Spectrophotometry, Ultraviolet
D002021:Buffers; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D003992:Dibucaine; D002045:Bupivacaine