High mineral affinity of polyphosphoester ionomer–phospholipid vesicles

Abstract

Bone-specific drug delivery is important for the treatment of osteoporosis and osseous metastases. However, there have been limitations in the design of drug carriers having bone affinity. We synthesized amphiphilic polyphosphoester ionomers (CH-PHE) and modified them to 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) vesicles. 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. In particular, the release of CF from DOPC vesicles containing 3% CH-PHE was most reduced. In addition, the enzymatic degradation of DOPC was reduced by immobilization with polyphosphoester ionomers; enzyme tolerance was increased with an increase in the molar fraction of polyphosphoester ionomers. Hemolytic activity of the phospholipid vesicles bearing CH-PHE was infrequently observed and was similar to that of the DOPC vesicles. Although a decrease in the viability of mouse osteoblastic cells (MC3T3-E1) in contact with the vesicles bearing CH-PHE was observed when the DOPC concentration of the vesicles bearing 20 mol % CH-PHE with highly ionized units was greater than 200 μM, the cytotoxicity was diminished by sodium salt formation of the CH-PHE. The affinity of the vesicles to calcium deposits generated by MC3T3-E1 cells was significantly improved by the immobilization polyphosphoesters.

Spontaneous Assembly into Pseudopolyrotaxane Between Cyclodextrins and Biodegradable Polyphosphoester Ionomers

“…For example, Xiong et al have reported that the degradation of polyphosphoesters is accelerated in the presence of alkaline phosphatase . Additionally, polyphosphoesters are found to show high binding affinity to bone tissues, thus considered to be candidates as fascinating biodegradable polymers possibly applied for hard tissue regenerations and drug delivery system. If we can utilize the polyphosphoesters as a degradable component of PRX, the potential bio­materials application of PRXs would be further expanded to novel biodegradable hydrogels and nanocarriers.…”

Bone Mineral Affinity of Polyphosphodiesters

“…Cholesterol (CH) is a major candidate as an initiator in the preparation of amphiphilic PPDEs because alcohols can be employed for organocatalytic ROP of cyclic phosphate monomers. Amphiphilic P(EP x /EEP y ) [CH-P(EP x /EEP y )] that was composed of EP and EEP units was first synthesized and immobilized on 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) vesicles (Figure 5b), which resulted in the zeta-potential becoming more negative with increasing amounts of immobilized CH-P(EP x /EEP y ) [30]. The stability of the vesicles was then effectively improved by surface modification and was controlled by changing the fraction of DOPC and CH-P(EP x /EEP y ).…”

Polyphosphoesters: New Trends in Synthesis and Drug Delivery Applications

“…Water‐soluble negatively charged polyphosphodiesters are also attractive polyelectrolyte materials. They can be achieved by selective hydrolysis of the pendant side chain which is a quite challenging reaction as the backbone integrity should be preserved. Interestingly, poly(phosphotriester) bearing allyl pendant groups can be easily converted into such polyelectrolyte by simple nucleophilic reaction, the allyl group playing the role of protecting group in this case (Scheme ).…”