Injectable microparticle-gel system for prolonged and localized lidocaine release. II. In vivo anesthetic effects.
Current treatment protocols for postoperative pain are beset by either the short duration of the anesthetic effect or requirement of hospitalization of the patients. We reported herein a novel treatment by applying to the surgical site a biodegradable microparticle-gel system for prolonged and localized release of encapsulated anesthetic drugs. In a previous publication, lidocaine-loaded poly(D,L-lactic acid) microspheres were fabricated and their formulations were optimized. In vitro characterization of these lidocaine-loaded microspheres, however, revealed a shortcoming of this system; that is, microspheres tend to fuse physically. Fusion of the microspheres could hinder their clinical applications, as it would clog the needle. In this article, we demonstrated that fabricating microspheres with high molecular weight (approximately 60 KDa) poly(lactic-co-glycolic acid) would increase the glass transition temperature of the microspheres after lidocaine loading, thereby increasing their mechanical stability and eliminating their fusion during storage. Such microspheres containing 31% (w/w) lidocaine in the presence or absence of 25% (w/v) poloxamer 407 gel were then evaluated in vivo by monitoring the sensory and motor functions of the rats after sciatic nerve block, using the previously established hot-plate and weight-bearing testing methods. Results showed that microspheres formulated with poloxamer 407 gel yielded the longest duration of sensory and motor block for a period of approximately 8.5 h, compared to 5 h by microspheres in saline, 5 h by lidocaine in poloxamer 407 gel, and 2 h by lidocaine in saline. This study suggests that the microsphere-gel system containing lidocaine could potentially be applied clinically to the treatment of postoperative pain.
College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor 48109-1065, USA.
Pen-Chung
PC
Chen
Daniel S
DS
Kohane
Yoon Jeong
YJ
Park
Robert H
RH
Bartlett
Robert
R
Langer
Victor C
VC
Yang
D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D010146:Pain / Q000378:metabolism / Q000517:prevention & control; D010147:Pain Measurement; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism
D000779:Anesthetics, Local; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D008012:Lidocaine