β-Casein is a 24 kDa amphiphilic milk protein. As such, β-casein self-organizes above the critical micellar concentration into nanometric micelles, constructed of hydrophobic core and a hydrophilic corona1. Core-shell polymeric micelles are very attractive candidates for drug delivery applications as potentially they can encapsulate large loads of hydrophobic guest molecules in the core, and provide enhanced stability, prolonged circulation times and controlled release2.
We designed β-casein micelles for oral drug delivery, and used as a model drug celecoxib, an anti-inflammatory hydrophobic drug. We developed a simple, fast, reproducible, and efficient formulation that allows encapsulation of very high loads3 of celecoxib. As indicated by XRD and NMR, the drug is present in the micelles in amorphous form, which is expected to facilitate drug penetration into the blood stream, resulting in increased drug bioavailability. In addition, our formulation can be lyophilized without the need of a cryoprotectant, and can be kept as a dry powder, providing long-term physical and chemical stability3. Importantly, we achieved loading efficiency >96%, thus eventually met the high daily dose of this drug in 1gr of the dry dosage, which potentially can be administered as a capsule. Alternatively, we proved fully reversible reconstitution of the structures by rehydration of the powder, making available drug administration also in liquid form.
Furthermore, in-vivo experiments in big animals showed our protein micellar nanocarriers successfully stabilize, deliver, and effectively release the drug at the intestine wall. Additionally, these studies demonstrated 3-fold improvement in drug bioavailability compared to the marketed formulation.
Research supervisor: Prof. Dganit Danino dganitd@tx.technion.ac.il
References
1. Portnaya, I., et al., Self-assembly of bovine beta-casein below the isoelectric pH. Journal of Agricultural and Food Chemistry, 2008. 56(6): p. 2192-2198.
2. Gao, Z.G., et al., Diacyllipid-polymer micelles as nanocarriers for poorly soluble anticancer drugs. Nano Letters, 2002. 2(9): p. 979-982.
3. Bachar, M., et al., Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled beta-casein micelles. Journal of Controlled Release, 2012. 160(2): p. 164-171.
