Hybrid Polyglycerols with Long Blood Circulation: Synthesis, Biocompatibility, and Biodistribution

• Published in: Macromolecular bioscience Vol. 14; no. 10; pp. 1469 - 1482
• Main Authors: Imran ul-haq, Muhammad, Lai, Benjamin F. L., Kizhakkedathu, Jayachandran N.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01-10-2014; Wiley Subscription Services, Inc
• Subjects: Animals; Biocompatibility; Biocompatible Materials - chemical synthesis; Biocompatible Materials - pharmacokinetics; Biocompatible Materials - pharmacology; biodistribution; Blood; Blood circulation; Blood Coagulation - drug effects; blood compatibility; Cell Survival - drug effects; cell viability; Complement Activation - drug effects; Drug delivery systems; Drug Delivery Systems - methods; Erythrocyte Aggregation - drug effects; Erythrocytes; Female; Glycerol - chemical synthesis; Glycerol - pharmacokinetics; Glycerol - pharmacology; Half-Life; Hemolysis - drug effects; Hemorheology; Human Umbilical Vein Endothelial Cells; Humans; linear-branched hybrid polyglycerol; Mice; Mice, Inbred BALB C; Molecular Weight; Nanostructures - chemistry; Platelet Activation - drug effects; Polyglycerols; Polymers; Polymers - chemical synthesis; Polymers - pharmacokinetics; Polymers - pharmacology; Synthesis; Tissue Distribution; Tritium; Viability; blood circulation; biodistribution; cell viability; blood compatibility; linear-branched hybrid polyglycerol
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201400152

Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M‾n ≈ 100 kDa) are synthesized with different compositions (15–80 mol% linear polyglycerol). Relatively small hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that they are highly compact functional nanostructures. The hybrid polyglycerols show excellent blood compatibility as determined by measuring their effects on blood coagulation, red blood cell aggregation, hemolysis, platelet, and complement activation. The cell viability in presence of hybrid polyglycerols is excellent up to 10 mg mL−1 concentration and is similar to both dextran and polyvinyl alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood circulation (t1/2β = 34 h) with minimal organ accumulation in mice. Multifunctionality, compact nature, biocompatibility, and the long blood circulation make these polymers attractive for the development of bioconjugates and drug delivery systems.
Hybrid polyglycerols (M‾n ≈ 100 kDa) with different compositions (15–80 mol% linear polyglycerol) with excellent blood and cell compatibility are synthesized. The polymers show long blood circulation with minimal organ accumulation in mice and are attractive for the development of multifunctional drug delivery systems.