Preparation and physicochemical characterization of biodegradable nerve guides containing the nerve growth agent sabeluzole.
The objective of this study was to develop and characterize a biodegradable drug-loaded nerve guide for peripheral nerve regeneration. Sabeluzole, a nerve growth agent, was selected as model compound. Four biodegradable polymers were selected for this study: a copolymer of polylactic acid and polycaprolactone (PCL); a copolymer of polyglycolic acid and polycaprolactone PCL; a copolymer of PCL/polydioxanone (PDO) and PDO. Placebo and drug loaded nerve guides were obtained by melt compression and melt extrusion. It was observed that melt compression and melt extrusion are feasible techniques to prepare the nerve guides. Based on the physicochemical characterization, all samples show absence of crystalline sabeluzole, indicating the formation of an amorphous dispersion. The in vitro release measurements show that the release of sabeluzole is complete, reproducible and can be controlled by the proper selection of the polymer. The release mechanism for all samples follows Fickian release behaviour.
Johnson & Johnson Pharmaceutical Research and Development, Drug Evaluation, Turnhoutseweg 30 2340 Beerse, Belgium. gverreck@prdbe.jnj.com
Geert
G
Verreck
Iksoo
I
Chun
Yufu
Y
Li
Ram
R
Kataria
Qiang
Q
Zhang
Joel
J
Rosenblatt
Annelies
A
Decorte
Koen
K
Heymans
Jef
J
Adriaensen
Monique
M
Bruining
Marie
M
Van Remoortere
Herman
H
Borghys
Theo
T
Meert
Jef
J
Peeters
Marcus E
ME
Brewster
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D001826:Body Fluids / Q000737:chemistry*; D004058:Diffusion; D004343:Drug Implants / Q000737:chemistry*; D004355:Drug Stability; D019544:Equipment Failure Analysis; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000737:chemistry; D009416:Nerve Regeneration / Q000187:drug effects; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000601:surgery; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011474:Prosthesis Design; D013696:Temperature; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry*
D001672:Biocompatible Materials; D004343:Drug Implants; D009414:Nerve Growth Factors; D010880:Piperidines; D011091:Polyesters; D011108:Polymers; D013844:Thiazoles; C016240:polycaprolactone; D019344:Lactic Acid; C033616:poly(lactide); C062968:lactide-caprolactone copolymer; C055163:sabeluzole