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Improving in vivo oral bioavailability of a poorly soluble drug: a case study on polymeric versus lipid nanoparticles

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Abstract

Poorly soluble drugs must be appropriately formulated for clinical use to increase the solubility, dissolution rate, and permeation across the intestinal epithelium. Polymeric and lipid nanocarriers have been successfully investigated for this aim, and their physicochemical properties, and in particular, the surface chemistry, significantly affect the pharmacokinetics of the drugs after oral administration. In the present study, PLGA nanoparticles (SS13NP) and solid lipid nanoparticles (SS13SLN) loaded with SS13, a BCS IV model drug, were prepared. SS13 bioavailability following the oral administration of SS13 (free drug), SS13NP, or SS13SLN was compared. SS13NP had a suitable size for oral administration (less than 300 nm), a spherical shape and negative zeta potential, similarly to SS13SLN. On the contrary, SS13NP showed higher physical stability but lower encapsulation efficiency (54.31 ± 6.66%) than SS13SLN (100.00 ± 3.11%). When orally administered (0.6 mg of drug), SS13NP showed higher drug AUC values with respect to SS13SLN (227 ± 14 versus 147 ± 8 µg/mL min), with higher Cmax (2.47 ± 0.14 µg/mL versus 1.30 ± 0.15 µg/mL) reached in a shorter time (20 min versus 60 min). Both formulations induced, therefore, the oral bioavailability of SS13 (12.67 ± 1.43% and 4.38 ± 0.39% for SS13NP and SS12SLN, respectively) differently from the free drug. These in vivo results confirm that the chemical composition of nanoparticles significantly affects the in vivo fate of a BCS IV drug. Moreover, PLGA nanoparticles appear more efficient and rapid than SLN in allowing drug absorption and transport to systemic circulation.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors acknowledge the GAUSS (Grandi Attrezzature Università di Sassari) core facility of the University of Sassari and Marzia Mureddu for TEM analysis.

Funding

This work was supported by the Sardinia Regional Government (FSC 2014–2020 programmes of Regione Autonoma della Sardegna; Grant numbers RASSR01499) and by the Foundation of Sardinia (Bando Fondazione di Sardegna – 2018–2020 e 2021 – Progetti di ricerca di base dipartimentali”; grant numbers J89J21015120005).

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Authors and Affiliations

  1. Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23/a, 07100, Sassari, Italy

    Giovanna Rassu, Antonella Obinu, Sandra Piras, Antonio Carta, Elisabetta Gavini & Paolo Giunchedi

  2. Department of Medicine, Surgery and Pharmacy, University of Sassari, viale San Pietro 43/B, 07100, Sassari, Italy

    Giovanna Rassu, Carla Serri, Sandra Piras, Antonio Carta, Elisabetta Gavini & Paolo Giunchedi

  3. Department of Life Sciences and Biotechnology, University of Ferrara, via Borsari 46, 44121, Ferrara, Italy

    Luca Ferraro

  4. Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, via Fossato di Mortara 19, 44121, Ferrara, Italy

    Alessandro Dalpiaz

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  1. Giovanna Rassu
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  2. Antonella Obinu
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  7. Elisabetta Gavini
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  9. Alessandro Dalpiaz
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Contributions

Elisabetta Gavini, Giovanna Rassu, and Paolo Giunchedi contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Antonella Obinu, Alessandro Dalpiaz, Luca Ferraro, and Carla Serri. Sandra Piras and Antonio Carta designed and synthesized the drug. Antonio Carta and Paolo Giunchedi acquired the funding. The first draft of the manuscript was written by Giovanna Rassu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Giovanna Rassu.

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All institutional and national guidelines for the care and use of laboratory animals were followed. This study was performed in accordance with the European Communities Council Directive of September 2010 (2010/ 63/EU). Approval was granted by the Ethics Committee of the University of Ferrara and by the Italian Ministry of Health (No 793/2018-PR).

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Rassu, G., Obinu, A., Serri, C. et al. Improving in vivo oral bioavailability of a poorly soluble drug: a case study on polymeric versus lipid nanoparticles. Drug Deliv. and Transl. Res. 13, 1128–1139 (2023). https://doi.org/10.1007/s13346-022-01278-4

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