Preparation and in vitro characterization of gentamycin-impregnated biodegradable beads suitable for treatment of osteomyelitis.
A new method for preparing poly(L-lactide) (PLA) biodegradable beads impregnated with an ionic aminoglycoside, gentamycin, is described. The process employs hydrophobic ion pairing to solubilize gentamycin in a solvent compatible with PLA, followed by precipitation with a compressed antisolvent (supercritical carbon dioxide). The resulting precipitate is a homogeneous dispersion of the ion-paired drug in PLA microspheres. The microspheres are approximately 1 microm in diameter and can be compressed into beads (3-6 mm in diameter) strung on surgical sutures for implantation. The bead strings exhibit no significant change in release kinetics upon sterilization with a hydrogen peroxide plasma (Ster-Rad). The kinetics of gentamycin release from the PLA beads are consistent with a matrix-controlled diffusion mechanism. While nonbiodegradable poly(methyl methacrylate) (PMMA) beads initially release gentamycin in a similar manner, the drug release from PMMA ceases after 8 or 9 weeks, while the PLA beads continue to release drug for over 4 months. Moreover, only 10% of the gentamycin is released from the PMMA beads, while PLA beads release more than 60% of their load, if serum is present in the release medium. The PLA system displays improved release kinetics relative to PMMA, is biodegradable, is unaltered by gas sterilization, can be used for a range of antibiotics, and can be manipulated without disintegration. These are all desirable properties for an implantable drug delivery system for the prevention or treatment of osteomyelitis.
Meyer
J D
JD
Department of Pharmaceutical Sciences, School of Pharmacy, Campus Box C238, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Falk
R F
RF
Kelly
R M
RM
Shively
J E
JE
Withrow
S J
SJ
Dernell
W S
WS
Kroll
D J
DJ
Randolph
T W
TW
Manning
M C
MC
D000042:Absorption; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry*; D010019:Osteomyelitis / Q000188:drug therapy; D011091:Polyesters / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D005839:Gentamicins; D011091:Polyesters; C033616:poly(lactide)