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Abstract Amphiphilic drugs are molecular drugs or drug conjugates possessing both hydrophilic and lipophilic properties. Representative amphiphilic drugs are composed of a pharmaceutical payload, a linker, and an appropriate amphiphilic modification. The physicochemical properties of amphiphilic drugs can be tailored by structure‐based engineering, which ultimately determine the drug molecules’ self‐assemble ability, bioavailability, protein binding, membrane anchoring, organ and intracellular distributions, side effects, and biological efficacy. Unlike the traditional carrier‐assistant drug delivery system, many of the amphiphilic drugs are carrier‐free and can self‐deliver to target sites/cells and access intracellular organelles without an external delivery carrier. This is achieved by molecular designs that control the delivery pathways of amphiphilic drugs at organ/tissue, cellular, and intracellular levels. In this review the recent advances in self‐delivery amphiphilic drugs and vaccines are highlighted, with emphasis on the underlying design principles and emerging applications.
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Predicting the frequencies of drug side effects
Abstract A central issue in drug risk-benefit assessment is identifying frequencies of side effects in humans. Currently, frequencies are experimentally determined in randomised controlled clinical trials. We present a machine learning framework for computationally predicting frequencies of drug side effects. Our matrix decomposition algorithm learns latent signatures of drugs and side effects that are both reproducible and biologically interpretable. We show the usefulness of our approach on 759 structurally and therapeutically diverse drugs and 994 side effects from all human physiological systems. Our approach can be applied to any drug for which a small number of side effect frequencies have been identified, in order to predict the frequencies of further, yet unidentified, side effects. We show that our model is informative of the biology underlying drug activity: individual components of the drug signatures are related to the distinct anatomical categories of the drugs and to the specific drug routes of administration.
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- Award ID(s):
- 1660648
- PAR ID:
- 10290037
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41467-020-18305-y
