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Polycaprolactone microparticles for the subcutaneous administration of cannabidiol: in vitro and in vivo release

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A Correction to this article was published on 22 December 2023

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Abstract

Cannabidiol (CBD) has become a highly attractive entity in therapeutics. However, its low aqueous solubility, instability and handling problems limit the development of effective CBD formulations. Subcutaneously administered CBD-loaded polycaprolactone microparticles (MP) represent an interesting strategy to overcome these challenges. This work focuses on evaluating the pharmacokinetics of CBD formulated in polymer microparticles for subcutaneous administration and characterising its release. The mean release time (MRLT) parameter is used to compare the release of CBD from two microparticle formulations in vitro and in a mouse model. After the administration of CBD in solution, a bicompartmental distribution is observed due to the extensive diffusion to the brain, being the brain/blood AUC ratio 1.29. The blood and brain mean residence time (MRT) are 0.507 ± 0.04 and 0.257 ± 0.0004 days, respectively. MP prepared with two drug/polymer ratios (15/150-MP and 30/150-MP) are designed, showing similar in vitro dissolution profiles (similarity factor (f2) is 63.21), without statistically significant differences between MRLTin vitro values (4.68 ± 0.63 and 4.32 ± 0.05 days). However, considerable differences in blood and brain profiles between both formulations are detected. The blood and brain MRT values of 15/150-MP are 6.44 ± 0.3 days and 6.15 ± 0.25 days, respectively, whereas significantly lower values 3.91 ± 0.29 days and 2.24 ± 0.64 days are obtained with 30/150-MP. The extended release of CBD during 10 days after a single subcutaneous administration is achieved.

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Data availability

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

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Acknowledgements

The authors would like to thank Qing Tao and the Spanish Center of Electron Microscopy for their technical assistance.

Funding

This work was partially funded by the Santander-UCM Research Group 910939; Parenteral Administration of Drugs. Dolores Hernán (AP2005-0184) has been granted a research fellow from the Spanish Ministry of Education.

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Authors and Affiliations

  1. Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain

    Ana Isabel Fraguas-Sánchez, Dolores Hernán & Ana Isabel Torres-Suárez

  2. Institute of Industrial Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain

    Ana Isabel Fraguas-Sánchez & Ana Isabel Torres-Suárez

  3. Department of Food and Pharmaceutical Sciences, San Pablo CEU University, Madrid, Spain

    Consuelo Montejo

  4. Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298-0613, USA

    Justin L. Poklis & Aron H. Lichtman

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  1. Ana Isabel Fraguas-Sánchez
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Contributions

Conceptualization: AIT-S; methodology: AIT-S, AHL; formal analysis and investigation: AIF-S, DH, JLP, CM; writing—original draft preparation: AIF-S, DH; writing—review and editing: AIT-S, AIF-S; funding acquisition: AIT-S; resources: AIT-S, AHL; supervision: AIT-S.

Corresponding author

Correspondence to Ana Isabel Torres-Suárez.

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Ethics approval and consent to participate

This study uses animals. It was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committees of the Complutense University of Madrid and Community of Madrid -Spain- (PROEX 148/17). The study does not involve human subjects.

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The authors declare no competing interests.

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Fraguas-Sánchez, A.I., Hernán, D., Montejo, C. et al. Polycaprolactone microparticles for the subcutaneous administration of cannabidiol: in vitro and in vivo release. Drug Deliv. and Transl. Res. 14, 959–969 (2024). https://doi.org/10.1007/s13346-023-01444-2

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