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

ABSTRACT: Many drug candidates fail therapeutic development because of poor aqueous solubility. We have conceived a computer-aided strategy to enable polymeric micelle-based delivery of poorly soluble drugs. We built models predicting both drug loading efficiency (LE) and loading capacity (LC) using novel descriptors of drug-polymer complexes. These models were employed for virtual screening of drug libraries, and eight drugs predicted to have either high LE and high LC or low LE and low LC were selected. Three putative positives, as well as three putative negative hits, were confirmed experimentally (implying 75% prediction accuracy). Fortuitously, simvastatin, a putative negative hit, was found to have the desired micelle solubility. Podophyllotoxin and simvastatin (LE of 95% and 87% and LC of 43% and 41%, respectively) were among the top five polymeric micelle-soluble compounds ever studied experimentally. The success of the strategy described herein suggests its broad utility for designing drug delivery systems.

SUBMITTER: Alves VM

PROVIDER: S-EPMC6594770 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Alves Vinicius M VM Hwang Duhyeong D Muratov Eugene E Sokolsky-Papkov Marina M Varlamova Ekaterina E Vinod Natasha N Lim Chaemin C Andrade Carolina H CH Tropsha Alexander A Kabanov Alexander A

Science advances 20190626 6

Many drug candidates fail therapeutic development because of poor aqueous solubility. We have conceived a computer-aided strategy to enable polymeric micelle-based delivery of poorly soluble drugs. We built models predicting both drug loading efficiency (LE) and loading capacity (LC) using novel descriptors of drug-polymer complexes. These models were employed for virtual screening of drug libraries, and eight drugs predicted to have either high LE and high LC or low LE and low LC were selected. ...[more]

PMID: 31249867

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

Publications

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

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