1 4 dioxane

Gefitinib (GFT) and O-desmethyl gefitinib (GFT-M2) were purchased from Quimigen. O-Desmorpholinopropyl gefitinib (GFT-M1) was purchased from Fluorochem. N-Acetyl-L-tyrosine methyl ester (NAc-TyrMe), N-acetyl-L-tryptophan methyl ester (NAc-TrpMe), anthracene, human serum albumin (HSA) and α₁-acid glycoprotein from human plasma (HAG) were purchased from Sigma-Aldrich. PBS Buffer was prepared by dissolving phosphate-buffered saline tablets (Sigma) using ultrapure water from a Millipore (Milli-Q Synthesis) system. Spectrophotometric solvents (acetonitrile, 1,4-dioxane, toluene and cyclohexane) were obtained from Scharlab and used without further purification.

Sulfuric acid (98%, Sigma Aldrich), phenol (crystallized extra pure, Scharlau), acetic anhydride (99%, sigma Aldrich), pyridine (99.5%, Scharlau), 1, 4-dioxane (99%, Scharlau), methylene blue (99%, scharlau) were used without any further treatment.
Spent coffee grounds was collected from local coffee shops and dried for 1 week in the dark. The residue was washed using distilled water in a Soxhlet apparatus in order to eliminate water soluble extractable then dried in an oven at 105 °C to remove residual moisture.

Poly(3-hydroxybutyrate−co−3−hydroxyhexanoate) with 11% of hydroxyhexanoate (HH) content (PHBH) and molecular weights of 500–600 kDa was kindly gifted by Kaneka Co, Brussels, Belgium. Dichloromethane, chloroform, dimethyl sulfoxide, 1,4 dioxane, poly(ethylene glycol) (PEG) with molecular weights of 200, 400, and 600 g/mol, were purchased from Scharlau, Barcelona, Spain. poly(ethylene glycol) (PEG) with molecular weight of 100 kDa was purchased from Sigma Aldrich, Bavaria, Germany. Dimethyl carbonate was purchased from Alfa Aesar, Kandel, Germany. Isosorbide (C6H10O4) with a purity of 98% was purchased from Acros Organics, Geel, Belgium. Glycerol diacetomonolaurate (Biocizer ®) with purity ≥ 95% was kindly gifted by Riken Vitamin Co, Tokyo, Japan. All chemicals were used without further purification.