TY - JOUR
T1 - Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics
AU - Curreri, Alexander M.
AU - Kim, Jayoung
AU - Dunne, Michael
AU - Angsantikul, Pavimol
AU - Goetz, Morgan
AU - Gao, Yongsheng
AU - Mitragotri, Samir
N1 - Funding Information:
A.M.C. and J.K. contributed equally to this work. The authors thank Dr. Kelly Arnett of the Harvard Medical School Center for Macromolecular Interactions for technical assistance with circular dichroism, Dr. Roderick Bronson DVM of the Rodent Pathology Core at Harvard Medical School for H&E image analysis. Authors also acknowledge funding and facility support from the Harvard John A. Paulson School of Engineering and Applied Sciences. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supporting Information.
Funding Information:
A.M.C. and J.K. contributed equally to this work. The authors thank Dr. Kelly Arnett of the Harvard Medical School Center for Macromolecular Interactions for technical assistance with circular dichroism, Dr. Roderick Bronson DVM of the Rodent Pathology Core at Harvard Medical School for H&E image analysis. Authors also acknowledge funding and facility support from the Harvard John A. Paulson School of Engineering and Applied Sciences. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supporting Information.
Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2023/3/3
Y1 - 2023/3/3
N2 - Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic-based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold-standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic-based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins.
AB - Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic-based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold-standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic-based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins.
KW - bioavailability
KW - biologics
KW - deep eutectic solvents
KW - ionic liquids
KW - monoclonal antibodies
KW - pharmacokinetics
KW - subcutaneous
UR - http://www.scopus.com/inward/record.url?scp=85146312172&partnerID=8YFLogxK
U2 - 10.1002/advs.202205389
DO - 10.1002/advs.202205389
M3 - Article
C2 - 36642846
AN - SCOPUS:85146312172
SN - 2198-3844
VL - 10
JO - Advanced Science
JF - Advanced Science
IS - 7
M1 - 2205389
ER -