While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.
The continuous use of nonsteroidal anti-inflammatory drugs such as ibuprofen frequently leads to some serious side-effects including stomach ulcers and bleeding. In this paper, two kinds of new biocompatible polyesters (PIGB, PIGH) and polyesteramide (PIGA) comprising biodegradable components (L-glutamic acid, 1,4-butanediol, and 1,6-hexanediol and 6-amino hexanol) and ibuprofen as pendant group have been prepared by the melting polycondensation. The chemical structures of the monomer and polymers are characterized by FTIR, 1 H NMR spectrum, GPC, and contact angle measurements. The drug loading of ibuprofen reaches very high level (35-37%) for PIGB, PIGH, and PIGA carriers. The free ibuprofen molecules are released in vitro from polymer carriers in a controlled manner without a burst release, different from the release pattern observed in the other drugencapsulated systems. It is also found that the different hydrophilicity among PIGB, PIGH, and PIGA plays a key role in the timecontrolled release of ibuprofen. In addition, the viability of HeLa cells after 48 h of incubation reaches more than 100%, indicating no cytotoxicity for PIGB, PIGH, and PIGA carriers.
While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.
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