title: Tunable drug delivery using chemoselective functionalization of hydrogels.
abstract: In the last decades interests on cleavable linkers are growing due to the need to develop controlled drug delivery systems in biochemical and therapeutic applications. The synthesis of hydrogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy for this aim. However with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small molecules through hydrogel pores. In this work, we propose the functionalization of polyethylene glycol (PEG) chains with two different pH-sensitive linkers, ester and hydrazone, and their application as building blocks of microwave-assisted hydrogels for controlled delivery of small hydrophilic drugs. As drug mimetic we used Rhodamine B, a harmless fluorophore with steric hindrance and reactive groups similar to many small hydrophilic drugs. At physiological and low basic conditions, the cleavability of ester and hydrazone spacer evidenced the possibility to delay the release of drugs from the scaffold compared to hydrogels where drug was entrapped within the network only due to its steric hindrance. The obtained release profiles were compared, underlining the opportunity to tune the release rate using the synthesized hydrogels.
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Mauri
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy. Electronic address: filippo.rossi@polimi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy. Electronic address: alessandro.sacchetti@polimi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sacchetti
mesh_terms: D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008872:Microwaves; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D012235:Rhodamines; D011092:Polyethylene Glycols; C029773:rhodamine B
keywords: Drug delivery; Functionalization; Hydrogels; Polymers