Sequential delivery of erlotinib and doxorubicin for enhanced triple negative Breast cancer treatment using polymeric nanoparticle.

Autor: Zhou Z; Chemical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, OH 45221-0012, USA., Kennell C; Chemical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, OH 45221-0012, USA., Jafari M; Chemical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, OH 45221-0012, USA., Lee JY; Chemical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, OH 45221-0012, USA. Electronic address: jooyoup@gmail.com., Ruiz-Torres SJ; Department of Cancer Biology, College of Medicine University of Cincinnati, Cincinnati, OH 45267-0521, USA., Waltz SE; Department of Cancer Biology, College of Medicine University of Cincinnati, Cincinnati, OH 45267-0521, USA; Research Service, Cincinnati Veteran Hospital Medical Center, Cincinnati, OH 45267-0521, USA., Lee JH; Biomedical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, OH 45221-0012, USA.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2017 Sep 15; Vol. 530 (1-2), pp. 300-307. Date of Electronic Publication: 2017 Aug 01.
DOI: 10.1016/j.ijpharm.2017.07.085
Abstrakt: Recent studies of signaling networks point out that an order of drugs to be administrated to the cancerous cells can be critical for optimal therapeutic outcomes of recalcitrant metastatic and drug-resistant cell types. In this study, a development of a polymeric nanoparticle system for sequential delivery is reported. The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties [i.e. epidermal growth factor receptor (EGFR) inhibitor, erlotinib (Ei), and doxorubicin (Dox)]. Dox is hydrophilic and was complexed with anionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), via ion pairing to form a hydrophobic entity. Then it was co-encapsulated with hydrophobic Ei in a poly(L-lactide)-b-polyethylene glycol (PLA-b-PEG) nanoparticle by nanoprecipitation. The complexation of Dox with DOPA greatly helps the encapsulation of Dox, and substantially reduces the release rate of Dox. This nanoparticle system was found to burst the release of Ei with a slow and sustained profile of Dox, which is an optimal course of administration for these two drugs as previously reported. The efficacy of this sequential delivery nanoparticle system was validated in vitro and its in vivo potential applicability was substantiated by fluorescent imaging of high tumor accumulation.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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