Cytotoxicity of poly(96L/4D-lactide): the influence of degradation and sterilization.
The cytotoxicity of poly(96L/4D-lactide) (PLA96), and of its accumulated degradation products, was investigated following different sterilization methods and pre-determined heat-accelerated degradation intervals. PLA96 samples sterilized by either steam, ethylene oxide, or gamma irradiation were left untreated (S0 samples), or were degraded for 30 h or 60 h (S30 and S60 samples) at 90 degrees C in water. Extracts of the samples and of the remaining degradation fluids (F30 and F60) were prepared. The toxicity of both unfiltered and filtered extracts was analyzed in a cell growth inhibition (CGI) assay and a lactate dehydrogenase (LDH) leakage assay. Physical analysis of the extracted samples and of the degradation fluids also was performed. The S0 extracts demonstrated no significant CGI. The CGI of the S30 extracts ranged from 37 to 78%, whereas the CGI of the S60 extracts ranged from 6 to 33%. The CGI of the F30 extracts ranged from 19 to 38% and the CGI of the F60 extracts was 98 to 123%. The LDH leakage assay only showed a high response to the unfiltered F60 extracts. Neither sterilization nor filtration appeared to influence the cytotoxicity of the extracts. Particle accumulation, however, might affect cell membrane permeability resulting in LDH leakage. The results of this study suggest that the cytotoxicity of PLA96 is related to the pH and possibly the osmolarity of the tested extracts. The pH and osmolarity, in turn, may depend on variations in the amounts of solubilized lactic acid and oligomers. These variations appear to result from degradation stage-dependent differences in crystallinity, molecular weight and molecular weight distribution of the PLA96 samples.
Cordewene
F W
FW
Department of Oral and Maxillofacial Surgery, University Hospital Groningen, The Netherlands. cordewener@uthscsa.edu
van Geffen
M F
MF
Joziasse
C A
CA
Schmitz
J P
JP
Bos
R R
RR
Rozema
F R
FR
Pennings
A J
AJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002850:Chromatography, Gel; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D013242:Sterilization
D011091:Polyesters; C033616:poly(lactide); D007770:L-Lactate Dehydrogenase