Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Li, Ziang; Lenk, Theodore I.; Yao, Letitia J.; Bates, Frank S.; Lodge, Timothy P.

doi:10.1021/acs.macromol.7b02297

Title: Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

Journal Article · Wed Jan 03 00:00:00 EST 2018 · Macromolecules

DOI:https://doi.org/10.1021/acs.macromol.7b02297· OSTI ID:1424788

Li, Ziang ^[1]; Lenk, Theodore I. ^[1]; Yao, Letitia J. ^[1];

^[1];

^[1]

Univ. of Minnesota, Minneapolis, MN (United States)

In this work, two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) statistical copolymers and a series of three poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)- b-polystyrene (PND-b-PS-C12) diblock polymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, in which the molecular weight of the thermoresponsive PND corona block was held constant while the polystyrene core block length was varied. The corona thickness and density of the micelles in phosphate-buffered saline (PBS, pH = 6.5) were quantified by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Two hydrophobic model drugs, phenytoin and nilutamide, were used to examine the drug-polymer interactions in aqueous solution. Intermolecular interactions between the diblock polymer micelle corona and both drugs were revealed by 2D 1H nuclear Overhauser effect spectroscopy (NOESY). The drug-polymer “binding” strength, quantified by diffusion ordered NMR spectroscopy (DOSY), increased as corona density of the diblock polymer micelle increased for both drugs. The in vitro dissolution of the amorphous solid dispersions was systematically investigated as a function of drug type, drug loading, and the solution-state assembly of the polymers by using either a selective or nonselective spray drying solvent. Forming micelles prior to spray drying significantly enhanced phenytoin dissolution and supersaturation maintenance for the diblock polymers by storing the drug molecules in the corona.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: The Dow Chemical Company; E.I. DuPont de Nemours & Co.; Northwestern University; USDOE Office of Science (SC); National Science Foundation (NSF); European Union’s Horizon 2020; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; DMR-0520547; 654000; DMR-1420013; S10OD011952

OSTI ID:: 1424788

Journal Information:: Macromolecules, Vol. 51, Issue 2; ISSN 0024-9297

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 30 works

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Title: Maintaining Hydrophobic Drug Supersaturation in a Micelle Corona Reservoir

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