Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization

Research output: Contribution to journalJournal articleResearchpeer-review

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Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization. / Fonte, Pedro; Araújo, Francisca; Seabra, Vítor; Reis, Salette; van de Weert, Marco; Sarmento, Bruno.

In: International Journal of Pharmaceutics, Vol. 496, No. 2, 30.12.2015, p. 850-62.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Fonte, P, Araújo, F, Seabra, V, Reis, S, van de Weert, M & Sarmento, B 2015, 'Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization', International Journal of Pharmaceutics, vol. 496, no. 2, pp. 850-62. https://doi.org/10.1016/j.ijpharm.2015.10.032

APA

Fonte, P., Araújo, F., Seabra, V., Reis, S., van de Weert, M., & Sarmento, B. (2015). Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization. International Journal of Pharmaceutics, 496(2), 850-62. https://doi.org/10.1016/j.ijpharm.2015.10.032

Vancouver

Fonte P, Araújo F, Seabra V, Reis S, van de Weert M, Sarmento B. Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization. International Journal of Pharmaceutics. 2015 Dec 30;496(2):850-62. https://doi.org/10.1016/j.ijpharm.2015.10.032

Author

Fonte, Pedro ; Araújo, Francisca ; Seabra, Vítor ; Reis, Salette ; van de Weert, Marco ; Sarmento, Bruno. / Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization. In: International Journal of Pharmaceutics. 2015 ; Vol. 496, No. 2. pp. 850-62.

Bibtex

@article{bf90c67d318248d0ba81991cac3b8658,
title = "Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization",
abstract = "The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10{\%} (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466nm, and a zeta potential ranging between -34 and -38mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91{\%} and 10-12{\%}, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87{\%}, compared to only 72{\%} in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83{\%}, 69{\%}, 70{\%}, 77{\%} and 74{\%}, respectively after 48h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60{\%} after 48h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization.",
author = "Pedro Fonte and Francisca Ara{\'u}jo and V{\'i}tor Seabra and Salette Reis and {van de Weert}, Marco and Bruno Sarmento",
note = "Copyright {\circledC} 2015 Elsevier B.V. All rights reserved.",
year = "2015",
month = "12",
day = "30",
doi = "10.1016/j.ijpharm.2015.10.032",
language = "English",
volume = "496",
pages = "850--62",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization

AU - Fonte, Pedro

AU - Araújo, Francisca

AU - Seabra, Vítor

AU - Reis, Salette

AU - van de Weert, Marco

AU - Sarmento, Bruno

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/12/30

Y1 - 2015/12/30

N2 - The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10% (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466nm, and a zeta potential ranging between -34 and -38mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91% and 10-12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83%, 69%, 70%, 77% and 74%, respectively after 48h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization.

AB - The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10% (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466nm, and a zeta potential ranging between -34 and -38mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91% and 10-12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83%, 69%, 70%, 77% and 74%, respectively after 48h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization.

U2 - 10.1016/j.ijpharm.2015.10.032

DO - 10.1016/j.ijpharm.2015.10.032

M3 - Journal article

C2 - 26474964

VL - 496

SP - 850

EP - 862

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 2

ER -

ID: 161588626