Cytotoxicity and genotoxicity of superporous hydrogel containing interpenetrating polymer networks.
The superporous hydrogel containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) interpenetrating polymer networks (SPH-IPN) that had been developed as an oral delivery vehicle for protein drugs was subject to cytotoxicity and genotoxicity testing, thus evaluating its biological safety in use. In a battery of cytotoxicity assays on RBL-2H3 and Caco-2 cells, the SPH-IPN caused minimal damage towards cell viability, lysosomal activity, and metabolic activity following both direct and indirect treatment. The SPH-IPN did not induce cell apoptosis or DNA breakage in the above cell lines; it did not increase micronucleus (MN) incidence in mouse bone marrow, either. Therefore, the SPH-IPN was preliminarily considered to be biocompatible and might be a safe carrier for protein drugs. In addition, using the HPLC method, residual acrylic acid, acrylamide, and glutaraldehyde in the SPH-IPN were quantified to be 1.4, 2.0, and below 0.2 ppm, respectively. Lack of these low molecular monomers and crosslinker that were mainly responsible for the toxicity provided evidence for the good biocompatibility of the SPH-IPN.
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
Lichen
L
Yin
Xin
X
Zhao
Liming
L
Cui
Jieying
J
Ding
Miao
M
He
Cui
C
Tang
Chunhua
C
Yin
D020106:Acrylamide / Q000633:toxicity; D000179:Acrylates / Q000633:toxicity; D000180:Acrylic Resins / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D020552:Comet Assay; D053938:DNA Fragmentation; D005976:Glutaral / Q000633:toxicity; D006801:Humans; D020100:Hydrogels / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008422:Materials Testing; D015162:Micronucleus Tests; D009153:Mutagens; D009499:Neutral Red; D014677:Pharmaceutical Vehicles / Q000737:chemistry / Q000633:toxicity*; D011108:Polymers / Q000737:chemistry / Q000633:toxicity*
D000179:Acrylates; D000180:Acrylic Resins; D020100:Hydrogels; D009153:Mutagens; D014677:Pharmaceutical Vehicles; D011108:Polymers; C542061:poly(acrylic acid-co-acrylamide)-O-carboxymethyl chitosan; D020106:Acrylamide; D009499:Neutral Red; D048271:Chitosan; D007770:L-Lactate Dehydrogenase; C036658:acrylic acid; D005976:Glutaral