Polycaprolactone

All chemicals were acquired from Sigma Aldrich, and their product numbers are listed below. Glutaraldehyde (Sigma Aldrich, #G5882), osmium tetroxide (1%, Sigma Aldrich, #75633), Phosphate buffer solution (Sigma Aldrich, #P5244), ethanol (Sigma Aldrich, #E7023), propylene oxide (Sigma Aldrich, #82320), epoxy embedding medium 812 substitute (Sigma Aldrich, #45345), polycaprolactone (Sigma-Aldrich, #440744), dichloromethane (Sigma Aldrich, #270997), N-N-Dimethylformamide (Sigma Aldrich, #319937), epoxy embedding medium hardener DDSA (Sigma Aldrich, #45346), epoxy embedding medium hardener MNA (Sigma Aldrich, #45347), epoxy embedding medium accelerator DMP 30 (Sigma Aldrich, #45348), polycaprolactone (Sigma-Aldrich, ##440744), acetic acid (#270725), formic acid (90%, #110854), pyridine (Sigma-Aldrich #270970).

Simvastatin (SIM) was kindly donated by Krka d.d. (Novo Mesto, Slovenia); polycaprolactone (PCL) of 14,000 daltons, polysorbate (Tween ^® 20), propylene glycol, and ascorbic acid (AA) were purchased from Sigma Aldrich, St. Louis, MO, USA. Lactose Mesh 200 donated by Lek d.d. (Slovenia), Nanocelullose (NCC, Cellu Force, Montreal, QC, Canada), and Florite R calcium silicate (CaSi, Tomita Pharmaceutical, Tokushima, Japan) were used as antiadhesives in spray drying experiments. Chloroform (Merck KGaA, Darmstadt, Germany) and purified water were used as O/W emulsion phases. The solvents used for U(H)PLC analysis were of HPLC grade. All other reagents used were of analytical grade. Water for UPLC analysis was purified using a Milli-Q system with a 0.22 Millipak 40 filter (Millipore, Cork, Ireland).

All chemicals were stored in an inert atmosphere of dry argon. Chloroform-d for NMR (99.8 atom % D, with 0.1 v/v% TMS, stabilized with silver), and toluene (99.85%, Extra Dry, over Molecular Sieves, AcroSeal®) were purchased from Acros Organics (Geel, Belgium) and used as received. Rac-LA (rac-lactide, 3,6-dimethyl-1,4-dioxane-2,5-dione), ZnEt₂ solution (15% diethylzinc in toluene), PGA (propyl gallate, 98%+), poly(d,l-lactide) (viscosity 0.68 dL/g), and polycaprolactone (average M_w ca. 14,000; average M_n ca. 10,000) were purchased from Sigma-Aldrich Co. (Poznan, Poland) and used as received. CL (ε-caprolactone, 6-caprolactone, 99%+) was purchased from Sigma-Aldrich Co. (Poznan, Poland) and stored over 5 A° molecular sieves. Dichloromethane (pure, 99%) and methanol (pure, 99.9%) were purchased from Chempur (Piekary Śląskie, Poland) and distilled before use.

Multiwalled carbon nanotube (MWCNT) with diameter 6 to 13 nm and length 2.5 to 20 μm procured from Sigma Aldrich (CAS number 308068-56-6) and polycaprolactone (Sigma Aldrich CAS number 24980-41-4 Mn 80000) were used to functionalise. To improve the solubility of the nanotubes in organic solutions, they were exposed to an acid - base treatment with HNO₃, NaOH and HCl for elimination of impurities¹⁶ . Functionalization of carbon nanotubes with calcium phosphates was carried out by aqueous precipitation process of calcium phosphates. The MWCNT in three concentrations were added in a solution of calcium hydroxide (Ca(OH)₂) 1 M, followed by dispersion in ultrasound for 20 minutes at an amplitude of 45 kHz and pulses 2:1 using the Sonics Vibra Cell VCX500 equipment. A solution of 0.6 M phosphoric acid was mixed to the previous solution u at a rate of 5 ml/min and a temperature of 90 °C for one hour and 25 °C for an additional hour with stirring of 400 rpm until reaching a pH value of 4.0. The resulting solution precipitated for 48 hours, filtered, washed and dried at 120 °C for 24 hours. The final concentration of carbon nanotubes was 0.5, 1.0 and 1.5 g/L. Ca(OH)₂ was obtained from natural aragonite (CaCO₃) at 82.5 wt% (fish otolith) according to the procedure described by Montañez et al.¹⁷

The following reagents were from Sigma-Aldrich, USA: polycaprolactone (PCL, Mn 70,000–90,000 g/mol); human serum albumin (HSA); 1,1,1,3,3,3-hexafluoroisopropanol (HFIP); dimethyl sulfoxide (DMSO); polyvinylpyrrolidone (PVP, M 360,000 g/mol); trifluoroethanol (TFE); polyethylene glycol (PEG, 20,000 g/mol); polyvinyl alcohol (PVA, 89,000–90,000 g/mol); and PBS. Sirolimus (SRL) was from Fujian Kerui Pharmaceutical Co. Ltd. (Fuiqng, 150301, China). Activated carbon AX-21 was from Anderson Development Company (Adrian, MI, USA).