PMID- 35268673 OWN - NLM STAT- MEDLINE DCOM- 20220317 LR - 20220317 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 27 IP - 5 DP - 2022 Feb 27 TI - Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System. LID - 10.3390/molecules27051572 [doi] LID - 1572 AB - 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. FAU - Sanders, Alyssa B AU - Sanders AB AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Zangaro, Jacob T AU - Zangaro JT AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Webber, Nakoa K AU - Webber NK AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Calhoun, Ryan P AU - Calhoun RP AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Richards, Elizabeth A AU - Richards EA AUID- ORCID: 0000-0003-0705-6405 AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Ricci, Samuel L AU - Ricci SL AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Work, Hannah M AU - Work HM AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Yang, Daniel D AU - Yang DD AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Casey, Kaitlyn R AU - Casey KR AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Iovine, Joseph C AU - Iovine JC AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Baker, Gabriela AU - Baker G AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Douglas, Taylor V AU - Douglas TV AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Dutko, Sierra B AU - Dutko SB AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Fasano, Thomas J AU - Fasano TJ AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Lofland, Sarah A AU - Lofland SA AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Rajan, Ashley A AU - Rajan AA AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Vasile, Mihaela A AU - Vasile MA AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Carone, Benjamin R AU - Carone BR AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. FAU - Nucci, Nathaniel V AU - Nucci NV AUID- ORCID: 0000-0001-8034-4492 AD - Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. AD - Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA. LA - eng GR - MCB-1942957/National Science Foundation/ GR - 61678-UR6/American Chemical Society/ PT - Journal Article DEP - 20220227 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 SB - IM MH - *Hydrophobic and Hydrophilic Interactions PMC - PMC8911823 OTO - NOTNLM OT - fluorescence spectroscopy OT - protein encapsulation OT - reverse micelle OT - viability COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2022/03/11 06:00 MHDA- 2022/03/18 06:00 PMCR- 2022/02/27 CRDT- 2022/03/10 15:30 PHST- 2021/10/31 00:00 [received] PHST- 2022/02/19 00:00 [revised] PHST- 2022/02/22 00:00 [accepted] PHST- 2022/03/10 15:30 [entrez] PHST- 2022/03/11 06:00 [pubmed] PHST- 2022/03/18 06:00 [medline] PHST- 2022/02/27 00:00 [pmc-release] AID - molecules27051572 [pii] AID - molecules-27-01572 [pii] AID - 10.3390/molecules27051572 [doi] PST - epublish SO - Molecules. 2022 Feb 27;27(5):1572. doi: 10.3390/molecules27051572.