Prolonged local anesthetic action through slow release from poly (lactic acid co castor oil).
OBJECTIVE
To evaluate a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(lactic acid co castor oil) in prolonging motor and sensory block when injected locally.


METHODS
The polyesters were synthesized from DL: -lactic acid and castor oil with feed ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10% bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR mice and the duration of sensory and motor nerve blockade was measured.


RESULTS
The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the incorporated bupivacaine during 1 week in vitro. Single injection of 10% bupivacaine loaded into this polymer caused motor block that lasted 24 h and sensory block that lasted 48 h.


CONCLUSIONS
Previously we developed a ricinoleic acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30 h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of effective doses of the incorporated local anesthetic agent and prolongs anesthesia to 48 h.
Sokolsky-Papkov
Marina
M
Department of Medicinal Chemistry and Natural Products, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Golovanevski
Ludmila
L
Domb
Abraham J
AJ
Weiniger
Carolyn F
CF
D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005260:Female; D006868:Hydrolysis; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010592:Pharmaceutic Aids / Q000138:chemical synthesis / Q000737:chemistry*; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D015203:Reproducibility of Results; D014783:Viscosity
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D010592:Pharmaceutic Aids; D011091:Polyesters; C539317:poly(lactic acid-co-castor oil); D019344:Lactic Acid; D002368:Castor Oil; D002045:Bupivacaine