Supporting Information. Toward Understanding Drug Incorporation and. Delivery from Biocompatible Metal-Organic

Transcription

1 Supporting Information Toward Understanding Drug Incorporation and Delivery from Biocompatible Metal-Organic Frameworks in View of Cutaneous Administration Sara Rojas, Isabel Colinet, Denise Cunha, Tania Hidalgo, Fabrice Salles, Christian Serre,, Nathalie Guillou, and Patricia Horcajada *,, Institut Lavoisier, CNRS UMR 818. UVSQ, Université Paris-Saclay. 45, Avenue Des Etats Unis 7835 Versailles Cedex, France. Institut Charles Gerhardt Montpellier, CNRS UMR 5253, UM, ENSCM, Place E. Bataillon, 3495 Montpellier cedex 5, France. Institut des Matériaux Poreux de Paris, FRE 2 CNRS Ecole Normale Supérieure. Ecole Supérieure de Physique et de Chimie Industrielles de Paris, PSL Research University, 24 rue Lhomond, 755 Paris, France. IMDEA Energy. Avenue Ramón de la Sagra 3, Móstoles-Madrid, Spain. S1

2 1. HPLC conditions a) b) Integrated area (mv) y = x R² = 1. (mg ml -1 ) Figure S1. (a) Calibration plot of standard by HPLC method, and (b) UV-vis spectra and chromatogram of. a) b) Integrated Area (uv/sec) area (mv) 18 1,8E ,6E ,4E ,2E+7 1,E+7 8 8,E+6 6 6,E+6 4 4,E+6 2 2,E+6 y = x R² = Ibuprofen (mg.ml -1 ) (mg ml -1 ) Figure S2. (a) Calibration plot of standard by HPLC method, and (b) UV-vis spectra and chromatogram of. Absorbance AU A AU Absorbance Minutes Retention time (min) nm Retention Minutes time (min) S2

3 a) b) Integrated area (mv) 3.5E+7 3.E+7 2.5E+7 2.E+7 1.5E+7 1.E+7 5.E+6.E+ y = x R² = AU 1,3,5-BTC (mg ml -1 ).8.6 AU.4.2 Figure S3. (a) Calibration plot of standard by HPLC method, and (b) UV-vis spectra and chromatogram of 1,3,5-BTC Minutes Retention time (min) a) b) Integrated area (mv) 3.E+7 2.5E+7 2.E+7 1.5E+7 1.E+7 5.E+6 y = x R² = 1. AU.8.E ,4-BDC (mg ml -1 ) AU Minutes Retention time (min) Figure S4. (a) Calibration plot of standard by HPLC method, and (b) UV-vis spectra and chromatogram of 1,4-BDC. S3

4 a) b) Integrated area (mv) Absorbance.12.1 ABTC (mg ml -1 ) AU AU.8.6 Figure S5. (a) Calibration plot of standard by HPLC method, and (b) UV-vis spectra and chromatogram of ABTC Minutes Retention time (min) S4

5 2. MIL- MIL- MIL-@ MIL-@ θ (º) Figure S6. XRPD patterns of desolvated MIL-, and, and their corresponding aspirin and ibuprofen loaded materials. XRPD patterns of the free drugs have been included for comparison. 2θ (º) S5

6 3. TGA After thermal treatment, residue analysis and proposed formulas are estimated to be the following (Note that the drug-loading content is also described by the encapsulation efficiency (EE), where EE(%) = ; Dt is the initial amount of drug present in the starting impregnation solution and Dl is the amount of loaded drug). 1. MIL-@ [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ](C 9 H 8 O 4 )(C 2 H 6 O) 1,1. EE: 25%. MIL-@ [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ](C 13 H 18 O 2 )(C 2 H 6 O) 1.2. EE: [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 9 H 8 O 4 ) 3 (C 2 H 6 O) 1.4. EE: [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 13 H 18 O 2 ) 3.7 (C 2 H 6 O).5. EE: [Fe 3 O(OH).88 Cl.12 (C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3 ](C 9 H 8 O 4 ).2 (C 2 H 6 O) 3.2. EE: [Fe 3 O(OH).88 Cl.12 (C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3 ](C 13 H 18 O 2 ).5 (C 2 H 6 O) 3.2. EE: 12.5%. Table S1. Total drug incorporated during the impregnation process (wt % and mol mol -1 ) and calculated encapsulation efficiency (%). MOF MIL- Drug Drug wt % (mol mol -1 ) 3.6 ±.9 (1.) 24.8 ±.8 (1.) 35.5 ± 3.2 (3.7) 25.5 ± 3.7 (3.) 13.6 ±.7 (.5) 4.4 ±.6 (.2) Encapsulation efficiency, EE (%) S6

7 Weight loss (%) Weight loss (%) MIL- MIL-@ MIL T (ºC) Weight loss (%) T (ºC) Figure S7. TGA for pristine MIL-, and matrixes, and their corresponding and loaded materials under air atmosphere. S7

8 4. N 2 sorption measurements at 77 K 8 7 V a /cm 3 (STP) g MIL- MIL-@ MIL-@ p/p V a /cm 3 (STP) g p/p 6 5 V a /cm 3 (STP) g p/p Figure S8. N 2 sorption isotherms at 77 K for empty MIL-, and solids, and their corresponding and loaded materials. Empty symbols correspond to the desorption branch. S8

9 Calculations of drug occupancy volumes. The volume occupied by one drug molecule inside the MOF was estimated by taking into account the variation of MOF pore volume after the drug encapsulation, and the total amount of loaded drug. The drug occupancy volume has been described as: ( ) = ( ) ( ) ( ) ( ) (Eq. 1) where is the pore volume after (1) and before (2) drug encapsulation (A 3 g -1 ), is the molecular weight of the dried MOF after (1) and before (2) drug encapsulation, is Avogadro constant, and n is the total amount of loaded drug (mol mol -1 ). S9

10 5- FTIR MIL- MIL-@ Figure S9. FTIR spectra of the desolvated MIL-, and matrixes, and their corresponding aspirin (bottom) and ibuprofen (top) loaded materials. The spectra of free aspirin and ibuprofen have been included for comparison Table S2. CO stretching band of the FTIR spectra of the pure drugs ( and ) and the loaded matrixes MIL- 127@, ν(co) (cm -1 ) Material/molecule encaps. encaps. (shift) (shift) Free 17 (acid) - Free (acid) and 175 (ester) MIL- 173 (+4) 1697 (+17) 172 (+2) 1752 (+2) 176 (+6) 1698 (+18)) 1779 (+29) S1

11 6- MOF degradation MOF degradation (%) MIL Time (d) Figure S1. MOFs degradation profiles in pure water at 37 C estimated as the ligand released from the MIL,, and solids. S11

12 7- Released drug (%) Time (d) Figure S11. Completed and released from the different MOFs in simulated cutaneous conditions (aqueous media at 37 ºC). a) b) [] (mg g -1 ) c) 15 y = 94.66x R² =.99 MIL-@ y = 81.24x R² = y = 2.64x R² = Time (h 1/2 ) 35 3 [] (mg g -1 ) 15 5 MIL-@ y = 53.2x R² = y = 28.5x R² y = 11.59x R² = Time (h 1/2 ) [] (mg g -1 ) y = 5.4x R 2 = Time (h) Figure S12. Fitting of the (a) and (b) delivery data to the Higuchi Model, and (c) fitting of the delivery data to an order zero kinetic. S12

13 @ MIL-@_del Figure S13. FTIR spectra of the desolvated MIL-, and, their corresponding drug loaded materials (MOF@drug) and the final solids obtained after the drug delivery (MOF@drug_del). S13

14 TGA after drug delivery Table S3. Proposed formula of the obtained materials before and after the drug delivery process after 3 days. Comparison of the remaining drug in the solids calculated by HPLC and TGA. Proposed formula MIL-@ i [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ](C 9 H 8 O 4 )(C 2 H 6 O) 1,1 f [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 1.96 ](H 2 O) 3.5 (Fe 2 O 3 ).6 MIL-@ i [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ](C 13 H 18 O 2 )(C 2 H 6 O) 1.2 f [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ](H 2 O) i [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 9 H 8 O 4 ) 3 (C 2 H 6 O) 1.4 f Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 9 H 8 O 4 ).27 (H 2 O) i [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 13 H 18 O 2 ) 3.7 (C 2 H 6 O).5 f [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ](C 13 H 18 O 2 ) 1.3 (H 2 O) i [Fe 3 O(OH).88 Cl.12 (C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3 ](C 9 H 8 O 4 ).2 (C 2 H 6 O) 3.2 f [Fe 3 O(C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3.5 (C 9 H 8 O 4 ).1 (C 2 H 6 O) i [Fe 3 O(OH).88 Cl.12 (C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3 ](C 13 H 18 O 2 ).5 (C 2 H 6 O) 3.2 f [Fe 3 O(C 16 N 2 O 8 H 6 ) 1,5 (H 2 O) 3 ](C 13 H 18 O 2 ).9 (H 2 O) 3 no released drug (%) HPLC TGA 1 ±.1 ±.2 9 ± ± ± ± 4 18 Weight loss (%) MIL- MIL-@ MIL-@_del MIL-@ T ( C) Weight loss T( C) Weight loss T (ºC) Weight loss (%) MIL- MIL-@ MIL-@_del MIL-@ T ( C) Weight loss (%) @ T ( C) T (ºC) Figure S14. TGA for pristine MIL-, and matrixes, their corresponding drug loaded solids (MOF@drug), and the final materials obtained after the delivery process (MOF@drug_del). Weight loss (%) @ S14

15 MIL θ (º) θ (º) θ (º) Figure S15. XRPD pattern of desolvated matrixes MIL-, and, their corresponding and loaded materials, and the final materials obtained after during delivery loaded @_del). S15

16 V a /cm 3 (STP) g MIL MIL-@_del 3 MIL-@ p/p V a /cm 3 (STP) g p/p V a /cm 3 (STP) g p/p V a /cm 3 (STP) g MIL- MIL-@_del MIL-@ p/p V a /cm 3 (STP) g p/p V a /cm 3 (STP) g p/p Figure S16. N 2 sorption isotherms at 77 K for empty MIL-(Fe), and, their corresponding and loaded materials (MOF@drug), and the final materials obtained after the drug delivery (MOF@drug_del). Empty symbols denote desorption Table S4. Variation of the micropore volume and specific surface of the and containing MOF solids. MOF MIL- Drug Before encapsulation V p (cm 3.g -1 ) S BET (m 2.g -1 ) After drug encapsulation V p (cm 3.g -1 ) S BET (m 2.g -1 ) After drug delivery V p (cm 3.g -1 ) S BET (m 2.g -1 ) S16

17 Figure S17. Configurations of the and in ((a) and (b), respectively) and ((c) and (d), respectively). The color code is: H: white, C: black, N: blue, Zr: cyan, Fe: mauve The configuration (d) is extracted from DFT calculations in contrast with the other ones obtained from GCMC. S17

18 Table S5. Qualitative summary comparing some properties of the 3 MOFs. MIL- Metal Fe (III) Zr (IV) Fe (III) Ligand source 1,3,5-benzenetricarboxylic acid 1,4-benzenedicarboxilic acid 3,3,5,5 -azobenzenetetracarboxylic acid Formula [Fe 3 O(H 2 O) 2 OH(C 9 H 3 O 6 ) 2 ] nh 2 O [Zr 6 O 4 (OH) 4 (C 8 O 4 H 4 ) 6 ] nh 2 O [Fe 3 O(OH).88 Cl.12 (C 16 N 2 O 8 H 6 ) 1.5 (H 2 O) 3 ] nh 2 O S BET (m 2 g -1 ) ~ 2 ~ Vp (cm 3 g -1 ) Porosity Hydrophobic/hydrophilic balance mesoporous cages (25 & 29 Å), accessible via microporous windows (~ Å and ~8.6 Å, respectively). octahedral (~11 Å) and tetrahedral cavities (~8 Å) accessible via triangular micropores (~5 7 Å) 1D channel system (~ 6 Å) and cages of ~ 1 Å, accessible through apertures of ~ 3 Å. Hydrophilic Hydrophobic Hydrophilic/hydrophobic S18