Nowadays, biodegradable polymers such as poly(lactic acid)(PLA), poly(D,L-lactic-coglycolic acid)(PLGA) and poly(ε-caprolactone)(PCL) remain the most common biomaterials to produce drug-loaded nanoparticles(NPs). Pip...Nowadays, biodegradable polymers such as poly(lactic acid)(PLA), poly(D,L-lactic-coglycolic acid)(PLGA) and poly(ε-caprolactone)(PCL) remain the most common biomaterials to produce drug-loaded nanoparticles(NPs). Pipemidic acid(PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst.PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare selfassembled NPs with PIP contents as high as 27%(w/w). The NPs were characterized by microscopy,DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs.展开更多
基金Financial support for this work was provided by the European Community through the Marie Curie ITN CycloN Hit Grant no.608407supported by a public grant overseen by the French National Research Agency (ANR) as part of the "Investissements d'Avenir" program (Labex Nano Saclay, reference: ANR-10-LABX-0035)by the ANR-14-CE08-0017 grant
文摘Nowadays, biodegradable polymers such as poly(lactic acid)(PLA), poly(D,L-lactic-coglycolic acid)(PLGA) and poly(ε-caprolactone)(PCL) remain the most common biomaterials to produce drug-loaded nanoparticles(NPs). Pipemidic acid(PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst.PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare selfassembled NPs with PIP contents as high as 27%(w/w). The NPs were characterized by microscopy,DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs.
