Physicochemical properties of epidermal growth factor receptor inhibitors and development of a nanoliposomal formulation of gefitinib.

Journal of Pharmaceutical Sciences
Brian J TrummerRobert M Straubinger

Abstract

Inhibitors of epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases show efficacy in cancers that are highly addicted to nonmutated EGF signaling, but off-target effects limit therapy. Carrier-based formulations could reduce drug deposition in normal tissues, enhance tumor deposition, and reduce free drug concentrations, thereby reducing the side effects. Therefore, the feasibility of developing nanoliposomal formulations of EGFR inhibitors was investigated. Gefitinib and erlotinib fluorescence was characterized as a tool for formulation development. Peak excitation was 345 nm and peak emission was 385-465 nm, depending upon the environment polarity. Emission was negligible in water but intense in nonpolar solvents, membranes, or bound to serum proteins. Cellular uptake and distribution could also be imaged by fluorescence in drug-resistant tumor spheroids. Gefitinib fluorescence characteristics enabled facile optimization of formulations. Although 4-6 mol % gefitinib could be incorporated in the liposome bilayer, 40-60 mol % could be encapsulated in stable, remote-loaded liposomes consisting of distearoylphosphatidylcholine-polyethylene glycol-distereoylphosphatidylethanolamine-cholesterol (9:1:5 mol:mol:mol). Drug le...Continue Reading

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Citations

Jul 17, 2012·Pharmaceutical Research·Tista Roy ChaudhuriRobert M Straubinger
Aug 20, 2015·Pharmaceutical Research·Chandraiah GoduguMandip Singh
Aug 15, 2013·Journal of Liposome Research·Abhijeet P PandeyPrashant K Deshmukh
May 31, 2017·Drug Development and Industrial Pharmacy·Kyung Mi YangKunhong Kim
Nov 26, 2015·Advanced Healthcare Materials·Anchala I KuruppuTracey D Bradshaw

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