Synthesis of amphiphilic polyphosphoester ionomers for surface modification of small unilamellar phospholipid vesicles

Abstract

Bone-specific drug delivery is important for the treatment of osteoporosis and osseous metastases. Bisphosphonates are currently the major drugs used in this treatment. The clinical action of bisphosphonates on bone has been clarified and the molecular structure has been improved in order to obtain higher efficiency. By mimicking the chemical structure of bisphosphonate, we have synthesized polyphosphoester ionomers to modify the surface of phospholipid vesicles as novel bone-specific drug carriers. The ring-opening copolymerization of cyclic phosphoester monomers bearing ethoxy and benzyloxy groups was performed by using cholesterol as an initiator. The deprotection of benzyl groups from the copolymers results in the production of amphiphilic polyphosphoester ionomers (CH-PHE).Small unilamellar vesicles (SUVs) composed of 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) vesicles mixed with CH-PHE were prepared. The ζ-potential of the vesicles was decreased by immobilization of CH-PHE; the amount was influenced by the structure and fraction of CH-PHE. The release rate of 5-carboxyfluorescein from the vesicles could be controlled by changing the fraction of DOPC and CH-PHE.

High mineral affinity of polyphosphoester ionomer–phospholipid vesicles

“…It was clarified that the stability of phospholipid bilayer structure was influenced by not only cholesterol but also by polyphosphoester ionomers. However, the destabilization of CH‐PHE(17) was also observed when the fraction of CH‐PHE(17) was greater than 3 mol % 42. It has been reported that CF release was enhanced under acidic conditions because the hydrophobicity of CF was increased in that condition 43.…”