Research ArticleHEALTH AND MEDICINE

Cheminformatics-driven discovery of polymeric micelle formulations for poorly soluble drugs

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Science Advances  26 Jun 2019:
Vol. 5, no. 6, eaav9784
DOI: 10.1126/sciadv.aav9784
  • Table 1 List of positive and negative hits with experimental values.

    NA, not available.

    NameWater solubilityConcentration (mg)Predicted by QSPRExperimental
    LE 80LC 10LC 20LC 30LE (%)LC (%)
    Positive hits
      PodophyllotoxinVery slightly soluble15NANANANA23.826.3
    10111158.737.0
    8111095.243.2
    4110095.627.7
    21100100.016.7
      RutinSlightly soluble15NANANANA3.95.6
    1011116.56.1
    8111045.126.5
    4111060.319.5
    2110074.513.0
      TeniposideInsoluble15NANANANA1.52.2
    1011116.15.7
    8111185.014.5
    4111076.123.3
    2110085.014.5
      DiosminSlightly soluble15NANANANAInsolubleInsoluble
    101111InsolubleInsoluble
    81110InsolubleInsoluble
    41110InsolubleInsoluble
    21100InsolubleInsoluble
    Negative hits
      OlanzapineInsoluble15NANANANA9.712.7
    1000006.15.8
    800004.13.2
    400007.02.7
    2000042.37.8
      SimvastatinInsoluble15NANANANA5.07.0
    10000019.916.6
    8000087.241.1
    4000074.623.0
    2000087.214.8
      SpironolactoneInsoluble15NANANANA3.44.9
    10000031.824.1
    8000020.914.3
    4000053.817.7
    2000082.914.2
      TamibaroteneInsoluble15NANANANA0.91.3
    1000002.01.9
    800009.97.4
    4000087.325.9
    2000089.715.2
  • Table 2 Top 15 compounds ranked by LE and LC for 8-mg drug versus 10-mg polymer.

    Compound nameLE % (mean)LC % (mean)
    ABT-26310044.4
    Podophyllotoxin95.243.2
    Etoposide91.83 ± 2.9242.33 ± 0.75
    Simvastatin87.241.1
    Efavirenz86.2340.82
    Cisplatin prodrug (C6)84.840.4
    VE-82280.17 ± 4.4826.65 ± 18.88
    PTX63.09 ± 42.1630.38 ± 18.54
    AZD536362.27 ± 1.9333.27 ± 0.68
    Cisplatin prodrug (C4)58.531.9
    Teniposide57.231.4
    Cisplatin prodrug (C10)53.6523.85
    AZD805550.828.9
    DTX46.40 ± 40.4318.99 ± 15.81
    Rutin45.126.5

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/6/eaav9784/DC1

    Description of platinum complexes

    Compiling all experimental data

    Fig. S1. Results of cluster analysis of 25 compounds tested alone at 8 mg.

    Fig. S2. Variable importance for the five models developed.

    Table S1. List of 25 compounds tested alone at 8 mg with their respective clusters, LE and LC (minimum, maximum, mean, and SD values), LogP, MW, and number of performed experiments.

    Table S2. List of three drugs with highest LE variability tested at 8 mg/ml.

    Table S3. Statistical characteristics of LC and LE QSPR models based on fivefold external cross-validation.

    Table S4. List of eight polymers used in this study with specification of block sizes and end group.

    Data file S1. Curated solubilization data for a single drug or a two-drug combination loaded into polymeric micelles. This file contains all the data on compound solubilization generated in this study subject to curation protocols as described in Materials and Methods.

    References (55, 56)

  • Supplementary Materials

    The PDF file includes:

    • Description of platinum complexes
    • Compiling all experimental data
    • Fig. S1. Results of cluster analysis of 25 compounds tested alone at 8 mg.
    • Fig. S2. Variable importance for the five models developed.
    • Table S1. List of 25 compounds tested alone at 8 mg with their respective clusters, LE and LC (minimum, maximum, mean, and SD values), LogP, MW, and number of performed experiments.
    • Table S2. List of three drugs with highest LE variability tested at 8 mg/ml.
    • Table S3. Statistical characteristics of LC and LE QSPR models based on fivefold external cross-validation.
    • Table S4. List of eight polymers used in this study with specification of block sizes and end group.
    • References (55, 56)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • Data file S1 (Microsoft Excel format). Curated solubilization data for a single drug or a two-drug combination loaded into polymeric micelles. This file contains all the data on compound solubilization generated in this study subject to curation protocols as described in Materials and Methods.

    Files in this Data Supplement:

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