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    Screening and Matching Polymers with Drugs to Improve Drug Incorporation and Retention in Nanoparticles

    Year: 2020

    Journal: Mol. Pharm., Volume 17, JUN 1, page 2083–2098

    Authors: Animasawun, Rashidat K.; Taresco, Vincenzo; Swainson, Sadie M. E.; Suksiriworapong, Jiraphong; Walker, David A.; Garnett, Martin C.

    Organizations: Tertiary Education Trust Fund (TETFUND) Nigeria; Engineering and Physical Sciences Research Council (EPSRC), Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines (School of Pharmacy, University of Nottingham) [EP/L01646X]; Mahidol University [3802, 10978]

    Keywords: poly(glycerol adipate); nanoparticles; drug loading; drug release; polymer-drug interaction

    Key challenges hindering the clinical translation of the use of nanoparticles (NP) for delivery of drugs to tumors are inadequate drug loading and premature drug release. This study focused on understanding the conditions required to produce nanoparticles that can reach their target site with sufficient drug loading and drug retention for effective pharmacological action. Etoposide, etoposide phosphate, and teniposide were screened against modified poly(glycerol) adipate (PGA) based polymers by monitoring drug release from 40% drug in polymer films and using Fourier transform infrared spectroscopy (FTIR) and contact angle measurements to help understand the release results. Polymers were matched with the specific drugs based on the interactions observed. NP were then prepared by an interfacial deposition method. NPs were characterized and resulted in drug loadings ranging from 3.5% and 5%, respectively, for etoposide phosphate and etoposide with PGA modified with stearate (PGA85%C18) up to 13.4% for teniposide with PGA modified with tryptophan (PGA50%Try) and drug release of just 22-35% over 24 h. Assessment of cytotoxicity showed that etoposide nanoparticles with PGA85%C18 were more potent than an equivalent amount of free drug. This screening method to match polymers to drugs to monitor based drug and polymer interactions thus resulted in the formulation of nanoparticles with higher drug loading and slower release and potential for further development for clinical applications.
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