title: Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules.
abstract: In this paper we report a novel approach to generate biodegradable polyglycerol nanogels on different length scales. We developed a mild, surfactant free inverse nanoprecipitation process to template hydrophilic polyglycerol nanoparticles. In situ crosslinking of the precipitated nanoparticles by bioorthogonal copper catalyzed click chemistry allows us to obtain size defined polyglycerol nanogels (100-1000nm). Biodegradability was achieved by the introduction of benzacetal bonds into the net points of the nanogel. Interestingly, the polyglycerol nanogels quickly degraded into low molecular weight fragments at acidic pH values, which are present in inflamed and tumor tissues as well as intracellular organelles, and they remained stable at physiological pH values for a long time. This mild approach to biodegradable polyglycerol nanogels allows us to encapsulate labile biomacromolecules such as proteins, including the therapeutic relevant enzyme asparaginase, into the protein resistant polyglycerol network. Enzymes were encapsulated with an efficacy of 100% and after drug release, full enzyme activity and structural integrity were retained. This new inverse nanoprecipitation procedure allows the efficient encapsulation and release of various biomacromolecules including proteins and could find many applications in polymer therapeutics and nanomedicine.
authors.affiliation: Freie Universität Berlin, Institute for Chemistry and Biochemistry, Takustr. 3, D-14195 Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Madeleine
authors.initials: M
authors.lastname: Witting
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Staegemann
authors.forename: Florian
authors.initials: F
authors.lastname: Paulus
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
authors.forename: Sarah
authors.initials: S
authors.lastname: Küchler
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D001215:Asparaginase / Q000008:administration & dosage / Q000378:metabolism; D011232:Chemical Precipitation; D003692:Delayed-Action Preparations / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D000080385:Nanogels; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D050091:Dendrimers; D000080385:Nanogels; D011108:Polymers; D011506:Proteins; C413692:polyethylene glycol polyethyleneimine nanogel; C043941:polyglycerol; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D001215:Asparaginase; D005990:Glycerol