Biocompatibility systemic toxicity testing

Biocompatibility and Toxicity Test Methods Used for Screening Absorbable Drug Delivery Systems s... 

Toxicity. Toxicity is foimd to be a minor problem and many vesicle systems have passed standard toxicity tests. The hydrophilic PEO block effectively screens the influence of the hydrophobic cores on timescales of the measured circulation half-life ri/2. With respect to long-time applications, PEE is structurally similar to low-density polyethylene, which is commonly used in implants and is generally considered bioinert (214). PB is also understood to be bioinert as it is commonly chosen for the hydrophobic block in triblock copoljuners (215,216). In a more prolonged model test of biocompatibility, nondiflferentiated C2C12 cells were incubated with poljunersomes. The cells remained well spread with no evidence of cytotoxicity. As shown by the Trypan blue exclusion assay, polymersomes had no significant effect on cell survival. 

Cyclodextrins appear to be extremely biocompatible. They are unable to significantly permeate biological membranes and are not absorbed by the gastrointestinal tract yet do not induce a response from the body s immune system. Tests on rats indicate that LD50 values for the most toxic parent compound, /7-cyclodextrin, are greater than 5 g per kg of body weight when administered orally and 0.5 g per kg of body weight when administered intravenously. This low level of toxicity, coupled to the cyclodextrins ability to form inclusion complexes, makes them ideal excipients in pharmaceutical formulations. 

Ionic liquids are often hygroscopic [371], and considerable amounts of water might "contaminate" the ionic liquid affecting its properties, especially the viscosity of the system [373-375]. Impurities in the ionic liquid (from its synthesis) might be a reason for its toxicity to the cells [376]. Biocompatibility tests using l-alkyl-3-methylpyridinium- or l-alkyl-3-methylimidazolium-based ionic liquids and baker s yeast have been performed [361], and their toxic effect for the cells was attributed to the amphiphilic nature of the cation [362,364,367,371,377-381]. Saccharomyces cerevi-siae tolerates [PFg] as a counterion better than [BFJ, which was more toxic to the cells [382]. Ionic liquids have also been used with inunobilized baker s yeast [364], and the toxicity of l-alkyl-3-methylimidazolium-based ionic liquids increased with the exposure time. 

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