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Article

Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use

by
Marianna Abate
1,†,
Lorena Scotti
2,†,
Valeria Nele
2,
Michele Caraglia
1,
Marco Biondi
2,
Giuseppe De Rosa
2,
Carlo Leonetti
3,
Virginia Campani
2,*,
Silvia Zappavigna
1 and
Manuela Porru
3
1
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy
2
Department of Pharmacy, University Federico II of Naples, Via Domenico Montesano, 49, 80131 Naples, Italy
3
Research and Advanced Technologies Department, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to the work.
Int. J. Mol. Sci. 2022, 23(9), 5138; https://doi.org/10.3390/ijms23095138
Submission received: 7 April 2022 / Revised: 28 April 2022 / Accepted: 29 April 2022 / Published: 5 May 2022
(This article belongs to the Special Issue Contribution of Cancer-Targeting Drugs toward Faster Clinical Application 2.0)
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Abstract

Self-assembling nanoparticles (SANPs) promise an effective delivery of bisphosphonates or microRNAs in the treatment of glioblastoma (GBM) and are obtained through the sequential mixing of four components immediately before use. The self-assembling approach facilitates technology transfer, but the complexity of the SANP preparation protocol raises significant concerns in the clinical setting due to the high risk of human errors during the procedure. In this work, it was hypothesized that the SANP preparation protocol could be simplified by using freeze-dried formulations. An in-depth thermodynamic study was conducted on solutions of different cryoprotectants, namely sucrose, mannitol and trehalose, to test their ability to stabilize the produced SANPs. In addition, the ability of SANPs to deliver drugs after lyophilization was assessed on selected formulations encapsulating zoledronic acid in vitro in the T98G GBM cell line and in vivo in an orthotopic mouse model. Results showed that, after lyophilization optimization, freeze-dried SANPs encapsulating zoledronic acid could retain their delivery ability, showing a significant inhibition of T98G cell growth both in vitro and in vivo. Overall, these results suggest that freeze-drying may help boost the industrial development of SANPs for the delivery of drugs to the brain.
Keywords: self-assembling nanoparticles; bisphosphonates; zoledronic acid; lyophilization; differential scanning calorimetry; glioblastoma; scale-up self-assembling nanoparticles; bisphosphonates; zoledronic acid; lyophilization; differential scanning calorimetry; glioblastoma; scale-up

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MDPI and ACS Style

Abate, M.; Scotti, L.; Nele, V.; Caraglia, M.; Biondi, M.; De Rosa, G.; Leonetti, C.; Campani, V.; Zappavigna, S.; Porru, M. Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use. Int. J. Mol. Sci. 2022, 23, 5138. https://doi.org/10.3390/ijms23095138

AMA Style

Abate M, Scotti L, Nele V, Caraglia M, Biondi M, De Rosa G, Leonetti C, Campani V, Zappavigna S, Porru M. Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use. International Journal of Molecular Sciences. 2022; 23(9):5138. https://doi.org/10.3390/ijms23095138

Chicago/Turabian Style

Abate, Marianna, Lorena Scotti, Valeria Nele, Michele Caraglia, Marco Biondi, Giuseppe De Rosa, Carlo Leonetti, Virginia Campani, Silvia Zappavigna, and Manuela Porru. 2022. "Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use" International Journal of Molecular Sciences 23, no. 9: 5138. https://doi.org/10.3390/ijms23095138

APA Style

Abate, M., Scotti, L., Nele, V., Caraglia, M., Biondi, M., De Rosa, G., Leonetti, C., Campani, V., Zappavigna, S., & Porru, M. (2022). Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use. International Journal of Molecular Sciences, 23(9), 5138. https://doi.org/10.3390/ijms23095138

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