Abstract
Fast in situ forming, chemically crosslinked hydrogels were prepared by the amidation reaction betweenN-succinimidyl ester end groups of multi-armed poly(ethylene glycol) (PEG) and amino surface groupsof poly(amido amine) (PAMAM) dendrimer generation 2.0. To control the properties of thePEG/PAMAM hydrogels, PEGs were used with different arm numbers (4 or 8) as well as differentlinkers (amide or ester) between the PEG arms and their terminal N-succinimidyl ester groups.Oscillatory rheology measurements showed that the hydrogels form within seconds after mixing thePEG and PAMAM precursor solutions. The storage moduli increased with crosslink density and reachedvalues up to 2.3 kPa for hydrogels based on 4-armed PEG. Gravimetrical degradation experimentsdemonstrated that hydrogels with ester linkages between PEG and PAMAM degrade within 2 days,2whereas amide-linked hydrogels were stable for several months. The release of two different modeldrugs (fluorescein isothiocyanate-dextran with molecular weights of 4·103and 2·106g/mol, FITCDEX4K and FITC-DEX2000K, respectively) from amide-linked hydrogels was characterized by aninitial burst followed by diffusion-controlled release, of which the rate depended on the size of the drug.In contrast, the release of FITC-DEX2000K from ester-containing hydrogels was governed mainly bydegradation of the hydrogels and could be modulated via the ratio between ester and amide linkages. Invitro cytotoxicity experiments indicated that the PEG/PAMAM hydrogels are non-toxic to mousefibroblasts. These in situ forming PEG/PAMAM hydrogels can be tuned with a broad range ofmechanical, degradation and release properties and therefore hold promise as a platform for the deliveryof therapeutic agents.