Effect of stabilizer concentration on parameters of poly(D,L-lactide-co-glycolide) nanoparticles produced by nanoprecipitation

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Abstract

Effect of the poly(vinyl alcohol) (PVA) concentration on the parameters of nanoparticles based on biodegradable poly(D,L-lactide-co-glycolide) (PLGA) copolymers prepared by nanoprecipitation was studied. It was observed that the value of hydrodynamic diameter of the PLGA particles remained unchanged and was about ~ 130–140 nm with varying of the PVA concentration from 2.5 to 15 mg/mL (the organic phase concentration was 5 mg/mL). Both the polydispersity index and electrokinetic potential (absolute values) have tend to decrease with an increase in the PVA concentration. It was found that loading content of hydrophobic model drug docetaxel in the PLGA particles as well as its in vitro cytotoxic activity against mice colorectal carcinoma CT26 and human lung fibroblast WI-38 cell lines are slightly affected be the PVA concentration. However, the PLGA particles produced with high PVA concentration are easily re-dispersed to initial size after their lyophilization both with and without cryo-protectant.

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E. V. Kuznetsova

Национальный исследовательский центр «Курчатовский институт»

Author for correspondence.
Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128

A. E. Tyurnina

Национальный исследовательский центр «Курчатовский институт»

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128

E. A. Konshina

Национальный исследовательский центр «Курчатовский институт»; Московский физико-технический институт (национальный исследовательский университет)

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128; Институтский пер., 9, Долгопрудный, 141701

A. A. Atamanova

Институт синтетических полимерных материалов им. Н.С. Ениколопова РАН

Email: kuznetsova.kate992@gmail.com
Russian Federation, ул. Профсоюзная, 70, 117393

K. T. Kalinin

Национальный исследовательский центр «Курчатовский институт»; Институт синтетических полимерных материалов им. Н.С. Ениколопова РАН

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128; ул. Профсоюзная, 70, 117393

S. V. Aleshin

Национальный исследовательский центр «Курчатовский институт»

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128

V. G. Shuvatova

Национальный исследовательский центр «Курчатовский институт»

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128

G. A. Posypanova

Национальный исследовательский центр «Курчатовский институт»

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128

S. N. Chvalun

Национальный исследовательский центр «Курчатовский институт»; Институт синтетических полимерных материалов им. Н.С. Ениколопова РАН

Email: kuznetsova.kate992@gmail.com
Russian Federation, пл. Академика Курчатова, 1, Москва, 123128; ул. Профсоюзная, 70, 117393

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2. Fig. 1. Dependences of the hydrodynamic diameter (Dh, nm) and polydispersity index (PI) of (a) PLGA-Sn and (b) PLGA-Bi nanoparticles on the concentration of the PVA stabilizer in the aqueous phase (PVS/water, mg/ml).

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3. Fig. 2. Dependences of the electrokinetic potential values ​​(ζ, mV) of PLGA nanoparticles on the concentration of the PVA stabilizer in the aqueous phase (PVS/water, mg/ml).

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4. Fig. 3. Dependences of the values ​​of the average hydrodynamic diameter (Dh, nm) (a, b), polydispersity index (PI) (c, d) and electrokinetic potential (ζ, mV) (d, e) of PLGA-Sn (left column) and PLGA-Bi (right column) nanoparticles on the concentration of the PVA stabilizer in the aqueous phase (PVS/water, mg/ml) immediately after production and after double purification.

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5. Fig. 4. Distributions of the light scattering intensity by the hydrodynamic diameters (Dh, nm) of DOC-loaded PLGA-Bi particles obtained at a concentration of the PVA stabilizer in the aqueous phase equal to (a) 1, (b) 5, (c) 10, and (d) 15 mg/ml: 1 – in the initial dispersion (before lyophilization), 2 – after lyophilization without a cryoprotector and subsequent redispersion in water, 3 – after lyophilization in the presence of the cryoprotector D(–)-mannitol and subsequent redispersion in water.

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6. Fig. 5. Cytotoxic effect on cell lines (a) CT26 and (b) WI-38 for: 1 – free DOC, 2 – DOC-containing PLGA-Bi nanoparticles obtained at SPVA/water = 1 mg/ml, 3 – DOC-containing PLGA-Bi nanoparticles obtained at SPVA/water = 5 mg/ml, 4 – DOC-containing PLGA-Bi nanoparticles obtained at SPVA/water = 10 mg/ml, 5 – DOC-containing PLGA-Bi nanoparticles obtained at SPVA/water = 15 mg/ml, 6 – unloaded PVA-stabilized PLGA-Bi nanoparticles (CPVA/water = 5 mg/ml), 7 – unloaded PLGA-Bi nanoparticles obtained without PVA.

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