Indomethacin ind

Indomethacin (IND) (Sigma-Aldrich,
Saint Louis, USA, and Hawkins Pharmaceutical group, Minnesota, USA)
was used as a model drug, and the bulk material was in the γ-form.
The amorphous form was prepared from the γ-form by quench cooling
the molten drug on a heat sink placed on ice. The resulting glass
was placed in a desiccator over dry silica gel for 30 min and then
ground into a powder with a mortar and pestle. The α-form was
prepared by dissolving the γ-form in ethanol at 80 °C and
thereafter adding Milli-Q water at room temperature to initiate precipitation.^{25 (link)} The δ-form was obtained by desolvation
of IND methanolate.^{26 (link)} The ε-form
was obtained from an amorphous IND suspension prepared with pH 6.8
phosphate buffer.^{27 (link)} The solid-state forms
were verified by Raman spectroscopy, Fourier transform infrared spectroscopy
and X-ray powder diffraction and are designated as the 0 timepoint
for offline measurements.

Poly(lactic acid) (PLA, MW 106000 g/mol) under the trade name of 4032D comprising around 2% D-LA was purchased from NatureWorks (USA). Hydroxyapatite (HA, medical grade, spherical powder, 10 μm in diameter) was purchased from the National Engineering Research Center for Biomaterials, Sichuan University. PAMAM-COOH (G3.5, MW 5560 g/mol), ALN-PAMAM-COOH (G3.5, 1.6 ALN on each PAMAM-COOH, MW 5930 g/mol), fluorescein isothiocyanate (FITC)-labelled ALN-PAMAM-COOH, 21-arm star-PDMAEMA (MW 149500 g/mol) and linear PDMAEMA were prepared according to our previous reports38 (link)42 (link). Indomethacin (IND) was purchased from Sigma-Aldrich. All other reagents and solvents were purchased from Tianjin Bodi Chemical Holding Company and were of analytical grade. Quartz crystal microbalance (QCM) electrodes (titanium/gold crystals, resonant frequency = 5 MHz) were bought from Stanford Research System Corporation (USA). A home-built QCM, constructed using a Model QCM 100 analogue controller (Stanford Research System Corp., USA) and an Agilent 53131A universal counter, was employed for the microgravimetric experiments. Ultrapure water produced from a Millipore system with a resistivity of 18.2 MΩ.cm was used throughout the study.

A two-part kit of platinum-catalyzed silicone elastomer, Gumosil AD-1 (liquid, two-component A + B, cross-linked by platinum catalyst polydimethylsiloxane, PDMS) was purchased from Silikony Polskie (Nowa Sarzyna, Poland) and used as a solid matrix former. Silicone oil SO (Q7-9120, kinematic viscosity of 350 cSt; Dow Corning, Wiesbaden, Germany), or polyethylene glycol PEG (M_w 300; Sigma-Aldrich, Steinheim, Germany) and propylene glycol PG (Sigma–Aldrich, Steinheim, Germany) were used as hydrophilic additives. Indomethacin IND (Sigma–Aldrich, Steinheim, Germany) was a model drug. Tritium-labelled water ³H₂O (37 MBq/g, 18 g/mol) and scintillation cocktail Opti-phase Hisafe 3 were purchased from Perkin Elmer (Walthman, MA, USA). All other reagents and solvents were of analytical grade and purchased from J.T. Baker (South Plainfield, NJ, USA). If needed, Milli-Q purified water was used (Millipore, Merck, Germany).