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Critical Aggregation Concentration Can Be a Predictor of Doxorubicin Delivery Performance of Self-Assembling Amphiphilic Peptides With Different Hydrophobic Tails Publisher Pubmed



Zanganeh S1, 5 ; Firoozpour L2 ; Salavatipour MS3 ; Sardari S4 ; Cohan RA5 ; Mohajel N6
Authors
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Authors Affiliations
  1. 1. Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
  3. 3. Stem Cells and Regenerative Medicine Innovation Center Kerman University of Medical Sciences Kerman, Iran
  4. 4. Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran
  5. 5. Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, 1316943551, Iran
  6. 6. Department of Molecular Virology, Pasteur Institute of Iran, Tehran, 1316943551, Iran

Source: Journal of Pharmaceutical Sciences Published:2024


Abstract

Amphiphilic peptides hold great potential as drug delivery systems. A popular peptide design approach has been to place amino acids in the peptide sequence based on their known properties. On the other hand, the directed discovery approach aims to screen a sequence space for a desired property. However, screening amphiphilic peptides for desirable drug delivery properties is not possible without a quantity that is predictive of these properties. We studied the predictive power of critical aggregation concentration (CAC) values on the drug delivery performance of a series of amphiphilic peptides with different hydrophobic tails and close CAC values. The CAC values were predicted by our previously developed model and doxorubicin was used as a model hydrophobic drug. All peptides showed close drug loading, entrapment efficiency, and release profile. They also formed similar spherical particles by assembling in reverse β-sheet arrangements regardless of drug presence. Moreover, the assembled particles were able to accumulate doxorubicin inside ordinary as well as drug-resistant breast cancer cells and enhance its toxicity up to 39 and 17 folds, respectively. It can be concluded that similar drug delivery properties displayed by the peptides can be attributed to their similar hydrophilic-lipophilic balance as reflected in their close CAC values. © 2024 American Pharmacists Association
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