Hyaluronic Acid-Conjugated pH-Sensitive Liposomes for Targeted Delivery of Prednisolone on Rheumatoid Arthritis Therapy

Abstract

Aim: The treatment of rheumatoid arthritis remains a challenge as available therapies still entail the risk of deleterious off-target effects. The present study describes hyaluronic acid-conjugated pH-sensitive liposomes as an effective drug delivery-targeting strategy to synovial cells. Materials & methods: Therapeutic, cytotoxic and targeting potential of developed liposomes were studied in vitro using macrophages and fibroblasts cell lines.Results & Conclusion: Results suggest an enhanced cellular uptake of conjugated liposomes, mainly mediated by caveolae- and clathrin-dependent endocytosis. In vitro release studies demonstrated that prednisolone was preferentially released under acidic conditions mimicking intracellular endosomal compartments. Overall, results revealed that conjugated pH-sensitive liposomes are a promising nanoapproach for the targeted delivery of prednisolone within inflamed synovial cells for rheumatoid arthritis treatment.

Keywords:

• corticosteroids
• fibroblasts
• hyaluronic acid
• macrophages
• pH-responsive liposomes

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgements

The authors are also grateful to R Fernandes (Histology and Electron Microscopy Service – Instituto de Biologia Molecular e Celular [HEMS-I3S], University of Porto) for his expertise and technical assistance with TEM and Manuela Barros for administrative and technical support.

Financial & competing interests disclosure

The authors thank the received financial support from EU (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013. This work was supported by FCT through the FCT PhD Programmes and by Programa Operacional Potencial Humano (POCH), specifically by the BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences). In this context, VM Gouveia and J Lopes-de-Araújo thank FCT and POCH for their PhD grants (PD/BD/128388/2017 and PD/BD/114012/2015, respectively). C Nunes also thanks FCT for the Investigator grant (IF/00293/2015) and respective exploratory project, which is in the framework of this work. SA Costa Lima thanks Operação NORTE-01-0145-FEDER-000011 for her Investigator contract. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.