Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 10, Pages 3609-3616Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00736
Keywords
biomedical applications; cross-linking; hydrogels; polymeric materials
Funding
- European Union's Seventh Framework Programme [631280-MC]
- Russell Berrie Nano technology Institute
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Injectable biomaterials play a critical role in many biomedical applications. These materials, however, often have limitations in mechanical and drug-eluting properties attributed to their high water content and the weak secondary forces holding them together. Here we describe a new injectable material based on two complementary water-free, prepolymers modified with succinimidyl carbonate (SC) or with NH2 end groups that form a stiff matrix upon mixing. Cross-linking involves an immediate reaction between PEG(4)- SC and PEG(4)-NH2 that forms carbamate bonds and a delayed reaction of PEG(4)-SC with hydroxyl functional groups that forms carbonate bonds. The mechanical properties, swelling, and erosion kinetics of this biomaterial can be fine-tuned by varying the ratio between the two prepolymers. Bovine serum albumin and poorly water-soluble free base doxorubicin were readily loaded into this system, resulting in a high drug loading content attributed to the absence of water in the formulation. Controlled release over a period of 1 to 30 days was observed, depending on mixture composition and drug properties. The injectable nature of the formulation, its tailored mechanical properties, the fact that it can be cross-linked by two separate mechanisms, and its ability to incorporate and release hydrophilic and hydrophobic drugs make it very attractive as a drug delivery system.
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