Screening and Matching Polymers with Drugs to Improve Drug Incorporation and Retention in Nanoparticles
- 1 June 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Molecular Pharmaceutics
- Vol. 17 (6), 2083-2098
- https://doi.org/10.1021/acs.molpharmaceut.0c00236
Abstract
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.Keywords
Funding Information
- Engineering and Physical Sciences Research Council (EP/L01646X)
- Mahidol University (Grant no. 3802, Project no. 10978)
- Tertiary Education Trust Fund
This publication has 52 references indexed in Scilit:
- Insights into Active Targeting of Nanoparticles in Drug Delivery: Advances in Clinical Studies and Design Considerations for Cancer NanomedicineBioconjugate Chemistry, 2019
- Poly(glycerol adipate) – indomethacin drug conjugates – synthesis and in vitro characterizationInternational Journal of Pharmaceutics, 2017
- Nanoparticles and targeted drug delivery in cancer therapyImmunology Letters, 2017
- Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment of glioblastomaJournal of Controlled Release, 2016
- Nanoparticle-mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseasesJournal of Controlled Release, 2016
- Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumorsJournal of Controlled Release, 2015
- Multiscale Modeling of Drug–Polymer Nanoparticle Assembly Identifies Parameters Influencing Drug Encapsulation EfficiencyJournal of Chemical Theory and Computation, 2015
- Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersionsEuropean Journal of Pharmaceutical Sciences, 2015
- Local drug delivery to the brainAdvanced Drug Delivery Reviews, 2002
- PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drugJournal of Controlled Release, 1999