Fluorinated PLGA Nanoparticles for Enhanced Drug Encapsulation and 19F NMR Detection

28 July 2021

AperTO - Archivio Istituzionale Open Access dell'Università di Torino

Original Citation:

Fluorinated PLGA Nanoparticles for Enhanced Drug Encapsulation and 19F NMR Detection

Published version:

DOI:10.1002/chem.202002078

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S-1

Supporting Information

Fluorinated PLGA Nanoparticles for Enhanced

Drug Encapsulation and

19

_{F-NMR Detection}

Giulia Neri,

_{Giuliana Mion,}

_{Andrea Pizzi,}

_{Linda Chaabane,}

_{Francesco Cellesi,}

_{Floryan De}

Campo,

_{Michele R. Chierotti,}

_{Roberto Gobetto,}

_{Min Li,̚ Piergiorgio Messa,̚ Pierangelo Metrangolo,}

and Francesca Baldelli Bombelli

†

_{Laboratory of Supramolecular and Bio-Nanomaterials (SupraBioNanoLab),Department of Chemistry,}

Materials, and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20131 Milan, Italy;

┘

_{Institute of Experimental Neurology (INSPE) and Experimental Imaging Center (CIS), IRCCS Ospedale San}

Raffaele, 20132 Milan, Italy

┼

_{Department of Chemistry, Materials, and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20131}

Milan, Italy

˧

_{Department of Chemistry and NIS Centre, Università di of Torino, via Giuria 7, 10125 Turin, Italy}

̚Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

┴

_{Solvay Specialty Polymers, Bollate, 20021 Milan, Italy.}

Supporting Information ... S1

Table S1 ... S2

Table S2 ... S2

Figure S1 ... S3

Table S3 ... S3

Figure S2 ... S4

Figure S3 ... S4

Figure S4 ... S5

Figure S5 ... S6

Figure S6 ... S6

Figure S7. ... S7

S-2

Table S1: Molecular number (Mn), Molecular weight (Mw) and Dispersity (Đ) relative to PLGA, purified PLGA, F3-PLGA and F9-PLGA.

The high values obtained for F9-PLGA are probably due to the interactions between the THF and the fluorine moieties of the polymer.

Polymer Acetone:Water (volume:volume) mL pH Nanoparticle Concentration (mg/mL) Z-average Particle Size (nm) PDI PLGA 1:1 6.4 10 61±5 0.14 F 3-PLGA 1:1 6.4 10 54±6 0.14 F₉-PLGA 1:1 6.4 10 58±6 0.15

Table S2: DLS analysis of NPs based on PLGA, F3-PLGA and F9- PLGA substrates. The NPs were formulate at same pH= 6.4 and

S-3

Figure S1:19_{F-NMR spectra of F}

9-PLGA_NPs formulated at the same amount of F9-PLGA (10mg) and acetone: water volume ratio (1:1),

but at different pH values (ranging from 6.4 to 8.0), are reported on the left. All spectra were tougher collected with a trifluoroethanol standard solution (TFA). The linear fit of the integrals of the peak normalized for the peak of the TFA is reported on the right.

Table S3: DLS analysis of NPs based on F9- PLGA. The NPs were formulate at same acetone: water volume ratio (1:1), but at different pH

values in the range form 6.4 up to 8.0. The DLS data were obtained at the same NP concentration 10mg/mL.

Polymer pH Nanoparticle Concentration (mg/mL) Z-average Particle Size (nm) PDI F₉-PLGA_NPs 6.4 10 58±6 0.15 F₉-PLGA_NPs 7.0 _{10 51±6 0.18} F₉-PLGA_NPs 7.4 10 43±5 0.12 F₉-PLGA_NPs 8.0 _{10 51±7 0.12}

S-4

Figure S2. ATR-FTIR spectra of F9-PLGA_NPs (red) and DEX@F9-PLGA_2 (green). FT-IR spectrum of DEX (violet). The characteristic

bands of F9-PLGA_NPs and DEX and DEX@F9-PLGA_2 are reported in table.

Figure S3. ATR-FTIR spectra of F9-PLGA_NPs (blue) and LEX@F9-PLGA_2 (red). FT-IR spectrum of LEF (violet). In table a reported

S-5

Figure S4. The 19_{F NMR spectra of DEX@F}

9PLGA_2 (A) and LEF@F9PLGA_2 (B) show the characteristic 19F signal of fluorinated F9

-PLGA. Moreover, the 19_{F signal of fluorinated of LEF at ~ -62ppm, is well observed in the} 19_{F NMR spectrum of LEF@F9PLGA_2 (B).}

T1 (ms) T2 (ms)

F₃PLGA_NPs _{537 122}

F₉PLGA_NPs 625 60

DEX@F₉PLGA_2 703 23

LEF@F₉PLGA_2 _{538 35}

Table S4. T1 and T2 values of F3PLGA_NPs, F9PLGA_NPs, DEX@F9PLGA_2 and LEF@F9PLGA_2 dispersions evaluated at

physiological pH are reported.

S-6

Figure S6. 1_H-13_{C (100.6 MHz) CPMAS SSNMR spectra of F9-NPs, LEF and LEF@F9-NPs, acquired at a spinning speed of 12 kHz. The}

inset shows the signals of LEF confirming its presence in the nanoparticles.

Figure S7. 19_F-13_{C (100.6 MHz) CPMAS SSNMR spectra of F9-NPs, LEF and LEF@F9-NPs, acquired at a spinning speed of 12 kHz. In}

this kind of experiment the magnetization is transferred from the 19_{F nuclei to the carbon atoms, instead of from the protons as in the}

standard cross-polarization. Hence, the obtained spectra show only the signals assigned to carbon atoms which are close to fluorine atoms, i.e. those of the –CF3 groups of the nanoparticles and LEF at 122.4 and 124.8 ppm, respectively. In the spectrum of LEF@F9-NPs, both

S-7

Figure S7. 19_{F (376.5 MHz) MAS SSNMR spectra of F}

9-NPs and LEF@F9-NPs, acquired at a spinning speed of 32 kHz to ensure the

averaging of the homonuclear dipolar coupling. A signal at -69.4 ppm is observed for the nanoparticles, whereas two different resonances (-60.7 and -59.5 ppm) are visible for the LEF molecule loaded into the NPs. The two signals indicate the presence of two different environments for LEF inside the nanoparticles, in agreement with the broad 13_{C resonance observed in the} 19_F-13_{C CPMAS spectrum of}

LEF@F9-NPs.

Figure S8. 19_{F (376.5 MHz) DQ MAS spectrum of F9-NPs (A) and LEF@F9_NPs (B), acquired at a spinning speed of 32 kHz and using}