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Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

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Abstract

The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

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Acknowledgments

The authors were especially grateful to Dr Margarita Vega-Holm for her assistance with FT-IR analysis. Part of this work was funded by the Consejería de Innovación, Junta de Andalucía (Spain) (Project No. P09-CTS-5029). L.M-B. and M.D-L. are also grateful for the financial support from Junta Andalucía and from IV Plan Propio of University of Seville. We specially thank Microscopy and Biology Services of CITIUS (University of Seville) for technical assistance with cytometry studies. This work was also supported by projects PTDC/EBB-BIO/101237/2008 and PEst-OE/SAU/UI4013/2011 from iMed.UL.

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Authors and Affiliations

  1. Departmento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/Profesor García González, 2, 41012, Seville, España

    Matilde Durán-Lobato, Lucía Martín-Banderas & Mercedes Fernández-Arévalo

  2. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal

    Matilde Durán-Lobato, Lídia M. D. Gonçalves & Antonio J. Almeida

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  1. Matilde Durán-Lobato
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  2. Lucía Martín-Banderas
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Correspondence to Lucía Martín-Banderas.

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Durán-Lobato, M., Martín-Banderas, L., Gonçalves, L.M.D. et al. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids. J Nanopart Res 17, 61 (2015). https://doi.org/10.1007/s11051-015-2875-y

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