Polymer− drug interactions in tyrosine-derived triblock copolymer nanospheres: a computational modeling approach
Open accessAbstract
A combination of molecular dynamics (MD) simulations and docking calculations was employed to model and predict polymer-drug interactions in self-assembled nanoparticles consisting of ABA-type triblock copolymers, where A-blocks are poly(ethylene glycol) units and B-blocks are low molecular weight tyrosine-derived polyarylates. This new computational approach was tested on three representative model compounds: nutraceutical curcumin, anticancer drug paclitaxel and prehormone vitamin D3. Based on this methodology, the calculated binding energies of polymer-drug complexes can be correlated with maximum drug loading determined experimentally. Furthermore, the modeling results provide an enhanced understanding of polymer-drug interactions, revealing subtle structural features that can significantly affect the effectiveness of drug loading (as demonstrated for a fourth tested compound, anticancer drug camptothecin). The present study suggests that computational calculations of polymer-drug pairs hold the potential of becoming a powerful prescreening tool in the process of discovery, development and optimization of new drug delivery systems, reducing both the time and the cost of the process.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
MD simulation could rank order drugs by their loading in polymeric micelles in good agreement with experimental data.
“MD simulation could also rank order drugs by their loading in polymeric micelles in a good agreement with experimental data.”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [206]
The Conclusion reports that a model combining MD simulations with docking calculations rank-ordered three drugs by experimentally observed maximum loading. The study tested tyrosine-derived polymeric nanospheres, not polymeric micelles, and does not establish that MD simulation alone produced the ranking. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCostache et al. used MD and docking to predict preferred drug orientation to polymer and rank curcumin, paclitaxel, and vitamin D3 by binding energies with specific micelles.
“For example, Costache et al. used a combination of MD and docking calculations which predict preferred orientation of a drug to a polymer for ranking three drugs (curcumin, paclitaxel and vitamin D3) by the energies of binding of with PEG-b-oligo(desaminotyrosyl-tyrosine octyl ester suberate)-b-PEG micelles [206].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [206]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A semiempirical free energy force field with charge‐based desolvation
Huey, R., Morris, G. M., Olson, A. J., & Goodsell, D. S. (2007) · Journal of Computational Chemistry · doi:10.1002/jcc.20634 · Cited by 2,246 · see citing works
Micellar Nanocarriers: Pharmaceutical Perspectives
Torchilin, V. P. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9132-0 · Cited by 1,910 · see citing works
Gelderblom, H. A. J., Verweij, J., Nooter, K., & Sparreboom, A. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00171-x · Cited by 1,659 · see citing works
Virtual Computational Chemistry Laboratory – Design and Description
Tetko, I. V., Gasteiger, J., Todeschini, R., Mauri, A., Livingstone, D. J., Ertl, P., Palyulin, V. A., Radchenko, E. V., Zefirov, N. S., Makarenko, A. S., et al. (2005) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-005-8694-y · Cited by 1,504 · see citing works
Nano-engineering block copolymer aggregates for drug delivery
Allen, C., Maysinger, D., & Eisenberg, A. (1999) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/s0927-7765(99)00058-2 · Cited by 1,358 · see citing works
Automated docking of substrates to proteins by simulated annealing
Goodsell, D. S., & Olson, A. J. (1990) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340080302 · Cited by 1,288 · see citing works
Polymer Therapeutics: Concepts and Applications
Haag, R., & Kratz, F. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200502113 · Cited by 1,119 · see citing works
Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4
Morris, G. M., Goodsell, D. S., Huey, R., & Olson, A. J. (1996) · Journal of Computer-Aided Molecular Design · doi:10.1007/bf00124499 · Cited by 1,045 · see citing works
Protein–ligand docking: Current status and future challenges
Sousa, S. F., Fernandes, P. A., & Ramos, M. J. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21082 · Cited by 1,007 · see citing works
Effective drug delivery by PEGylated drug conjugates
Greenwald, R. B., Choe, Y. H., McGuire, J., & Conover, C. D. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00180-1 · Cited by 870 · see citing works
Albumin-bound paclitaxel: a next-generation taxane
Gradishar, W. J. (2006) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.7.8.1041 · Cited by 706 · see citing works
Engineered nanoparticles as precise drug delivery systems
Yih, T. C., & Al-Fandi, M. G. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20796 · Cited by 393 · see citing works
Liu, J., Xiao, Y., & Allen, C. (2004) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10533 · Cited by 358 · see citing works
Hierarchical Docking of Databases of Multiple Ligand Conformations
Lorber, D. M., & Shoichet, B. K. (2005) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026054637683 · Cited by 145 · see citing works
Watanabe, M., Kawano, K., Yokoyama, M., Opanasopit, P., Okano, T., & Maitani, Y. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.10.030 · Cited by 128 · see citing works
Nanoparticulate biopolymers deliver insulin orally eliciting pharmacological response
Reis, C. P., Veiga, F., Ribeiro, A. J., Neufeld, R. J., & Damgé, C. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21347 · Cited by 98 · see citing works
Patel, S., Lavasanifar, A., & Choi, P. (2008) · Biomacromolecules · doi:10.1021/bm800320z · Cited by 92 · see citing works
Machine Learning Methods and Docking for Predicting Human Pregnane X Receptor Activation
Khandelwal, A., Krasowski, M. D., Reschly, E. J., Sinz, M., Swaan, P. W., & Ekins, S. (2008) · Chemical Research in Toxicology · doi:10.1021/tx800102e · Cited by 71 · see citing works
Sheihet, L., Piotrowska, K., Dubin, R. A., Kohn, J., & Devore, D. I. (2007) · Biomacromolecules · doi:10.1021/bm060860t · Cited by 70 · see citing works
Self-citationNanoparticles loaded with ferrocenyl tamoxifen derivatives for breast cancer treatment
Anh, N. T. V., Marsaud, V., Bouclier, C., et al. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.06.033 · Cited by 69 · see citing works
Feng, S., Li, M., Chen, B., et al. (2002) · Materials Science and Engineering C · doi:10.1016/s0928-4931(02)00017-6 · Cited by 50 · see citing works
A multi-scale stochastic drug release model for polymer-coated targeted drug delivery systems
Haddish‐Berhane, N., Nyquist, C., Haghighi, K., et al. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.09.046 · Cited by 43 · see citing works
Allen, D. D., & Geldenhuys, W. J. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.06.004 · Cited by 37 · see citing works
In silico study on the effects of matrix structure in controlled drug release
Villalobos, R., Cordero-Sánchez, S., Vidales, A. M., et al. (2005) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2005.11.009 · Cited by 32 · see citing works
Akagi, T., Ueno, M., Hiraishi, K., et al. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.09.014 · Cited by 24 · see citing works
Feng, S., Huang, G., & Mu, L. (2000) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v29n5p633 · Cited by 16 · see citing works
Costache, A. D., Trawick, D., Bohl, D., et al. (2007) · Xenobiotica · doi:10.1080/00498250601089162 · Cited by 12 · see citing works
Self-citationBinary polymeric blends to microencapsulate nitroflurbiprofen: Physicochemical and in silico studies
Cilurzo, F., Selmin, F., Vistoli, G., et al. (2007) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2007.03.010 · Cited by 9 · see citing works
Akagi, T., Baba, M., & Akashi, M. (2007) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.127.307 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hwang, D., Ramsey, J. D., & Kabanov, A. V. (2020) · Advanced drug delivery reviews · doi:10.1016/j.addr.2020.09.009 · Cited by 699 · see citing works
Computational amphiphilic materials for drug delivery
Thota, N., & Jiang, J. (2015) · Frontiers in Materials · doi:10.3389/fmats.2015.00064 · Cited by 38 · see citing works
- Authors
- Costache, A. D., Sheihet, L., Zaveri, K., Knight, D. D., & Kohn, J.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Kohn, Joachim
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-08-18
- Volume
- 6
- Issue
- 5
- Pages
- 1620-1627
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC2758936
- OpenAlex
- W2061531844
- Cited by
- 79
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 8 · 2015: 6 · 2014: 6 · 2013: 7 · 2012: 4
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (P41EB001046)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Block Copolymer Self-Assembly
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Keywords
- drug-polymer interactions, triblock copolymers, polyethylene glycol, nanoparticle self-assembly, drug loading, curcumin, paclitaxel, vitamin D3, camptothecin, binding energy, drug delivery systems, molecular docking, molecular dynamics simulation
- MeSH terms
- Binding Sites, Cholecalciferol, Curcumin, Drug Carriers, Drug Interactions, Models, Molecular, Molecular Conformation, Polymers, Thermodynamics, Tyrosine, Molecular Structure, Drug Delivery Systems, Paclitaxel, Nanospheres
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
