Abstract
Polyphosphoesters (PPEs) are a class of versatile degradable polymers. Despite the high potential of this class of polymers in biomedical applications, little is known about their blood interaction and compatibility. We evaluated the hemocompatibility of water-soluble PPEs (with different hydrophilicities and molar masses) and PPE-coated model nanocarriers. Overall, we identified high hemocompatibility of PPEs, comparable to poly(ethylene glycol) (PEG), currently used for many applications in nanomedicine. Hydrophilic PPEs caused no significant changes in blood coagulation, negligible platelet activation, the absence of red blood cells lysis, or aggregation. However, when a more hydrophobic copolymer was studied, some changes in the whole blood clot strength at the highest concentration were detected, but only concentrations above that are typically used for biomedical applications. Also, the PPE-coated model nanocarriers showed high hemocompatibility. These results contribute to defining hydrophilic PPEs as a promising platform for degradable and biocompatible materials in the biomedical field.
Highlights
Polyphosphoesters (PPEs) belong to the few polymer classes that enable the synthesis of well-defined and degradable watersoluble polymers.[1,2] The presence of pentavalent phosphorous in the main chain allows for tuning the polymer properties by varying the lateral group, providing the polymers with high versatility
The PPE-coated nanocarriers were prepared by azaMichael addition between the amino group on the polystyrene surface and poly(ethyl ethylene phosphonate) (PEtEP), which was previously ω-functionalized with commercial 4(maleinimido)phenyl isocyanate (Figure 1)
We report a systematic study of blood compatibility for a set of hydrophilic PPEs with different hydrophilicities and molar masses
Summary
Polyphosphoesters (PPEs) belong to the few polymer classes that enable the synthesis of well-defined and degradable watersoluble polymers.[1,2] The presence of pentavalent phosphorous in the main chain allows for tuning the polymer properties (e.g., hydrophilicity, crystallinity, degradability, thermal stability, and so forth) by varying the lateral group, providing the polymers with high versatility. Several studies have reported the hydrolytic and enzymatic degradation of PPEs in vitro,[3,4] and PPE-containing (co)polymers were reported as noncytotoxic against different cell lines even at high concentrations.[1] In addition, hydrophilic PPE-coated nanocarriers exhibit a so-called “stealth effect,” and their cellular uptake can be controlled depending on the polymer hydrophilicity.[5] Based on such results, PPEs have been proposed for different biomedical applications, for example, protein− polymer conjugates,[6−8] nanocarriers loaded with drugs,[9] antimicrobial agents,[10] gene vectors,[11] or hydrogels for tissue engineering.[12] In many applications, PPEs are proposed as biodegradable alternatives to poly(ethylene glycol) (PEG),[1,13,14] which is nowadays the most used water-soluble polymer in nanomedicine to prolong the drug lifetime and efficiency.[15] In this context, the evaluation of PPE blood compatibility is an important step to translate these in vitro results to in vivo applications. Lower cytotoxicity compared to the commonly used Pluronic F127 analogues was detected.[16] A systematic blood compatibility study of different PPEs has not been reported to date. The results were compared to those of PEG, aiming at detecting any difference in the hemocompatibility in view of future medical applications
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