Thermoresponsive nanogels for prolonged duration local anesthesia.
Nanogels based on poly(N-isopropylacrylamide) are attractive vehicles for prolonged duration local anesthesia because of their tunable size, number of functional groups, thermoresponsiveness and anionic charge. Nerve block durations of up to 9h were achieved using acrylic acid-loaded nanogels loaded with bupivacaine. Increasing the anionic charge density of the nanogels or (for more highly acid-functionalized nanogels) decreasing the nanogel size facilitated longer duration of anesthetic release. Small (<300 nm diameter) nanogels formed dense aggregates upon injection in vivo and induced only mild inflammatory responses, while large (>500 nm diameter) nanogels typically remained as liquid-like residues in vivo and induced more severe inflammatory reactions.
Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.
Todd
T
Hoare
Stuart
S
Young
Michael W
MW
Lawlor
Daniel S
DS
Kohane
D016475:3T3 Cells; D000772:Anesthesia, Local; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007267:Injections; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects; D000080385:Nanogels; D009407:Nerve Block; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D011984:Sensory Receptor Cells / Q000187:drug effects; D013194:Staining and Labeling; D013696:Temperature; D013997:Time Factors
D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002045:Bupivacaine