In Situ Dual Cross-Linking of Neat Biogel with Controlled Mechanical and Delivery Properties

5 years ago

In Situ Dual Cross-Linking of Neat Biogel with Controlled Mechanical and Delivery Properties

Regina Kelmansky, Boaz Mizrahi, Maayan Lufton, Alona Shagan, Boris Rozenblit, Rawan Omar

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 PEG₄–SC and PEG₄–NH₂ that forms carbamate bonds and a delayed reaction of PEG₄–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.

Publisher URL: http://dx.doi.org/10.1021/acs.molpharmaceut.7b00736

DOI: 10.1021/acs.molpharmaceut.7b00736