Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System |
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Authors: | Alyssa B. Sanders Jacob T. Zangaro Nakoa K. Webber Ryan P. Calhoun Elizabeth A. Richards Samuel L. Ricci Hannah M. Work Daniel D. Yang Kaitlyn R. Casey Joseph C. Iovine Gabriela Baker Taylor V. Douglas Sierra B. Dutko Thomas J. Fasano Sarah A. Lofland Ashley A. Rajan Mihaela A. Vasile Benjamin R. Carone Nathaniel V. Nucci |
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Affiliation: | 1.Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA; (A.B.S.); (J.T.Z.); (N.K.W.); (R.P.C.); (E.A.R.); (D.D.Y.); (K.R.C.); (G.B.); (T.J.F.); (A.A.R.); (M.A.V.); (B.R.C.);2.Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA; (S.L.R.); (H.M.W.); (J.C.I.); (T.V.D.); (S.B.D.); (S.A.L.) |
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Abstract: | Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems. |
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Keywords: | protein encapsulation reverse micelle viability fluorescence spectroscopy |
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