Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery
by
Giovanna Rassu 1,†
, Silvia Fancello 2,†, Marta Roldo 3, Milo Malanga 4, Lajos Szente 4, Rossana Migheli 2,*, Elisabetta Gavini 1,* and Paolo Giunchedi 1
Giovanna Rassu 1,†, Silvia Fancello 2,†, Marta Roldo 3, Milo Malanga 4, Lajos Szente 4, Rossana Migheli 2,*, Elisabetta Gavini 1,* and Paolo Giunchedi 1
1
Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23/a, 07100 Sassari, Italy
2
Department of Medical, Surgical and Experimental Sciences, University of Sassari, viale San Pietro 43/b, 07100 Sassari, Italy
3
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK
4
CycloLab Ltd., Illatos út 7, H-1097 Budapest, Hungary
*
Authors to whom correspondence should be addressed.
â€
These authors contributed equally to this work.
Pharmaceutics 2020, 12(7), 658; https://doi.org/10.3390/pharmaceutics12070658
Received: 22 June 2020 / Revised: 8 July 2020 / Accepted: 10 July 2020 / Published: 12 July 2020
(This article belongs to the Special Issue Nose to Brain Delivery (Volume II))
Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than their parent, cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable materials for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal- and epithelial-type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as nontoxic. Based on these results, a fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cell protection against oxidative stress.
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Keywords:
cationic cyclodextrin; cyclodextrin polymer; epichlorohydrin cross-linker; nasal delivery; cytotoxicity; cell uptake
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MDPI and ACS Style
Rassu, G.; Fancello, S.; Roldo, M.; Malanga, M.; Szente, L.; Migheli, R.; Gavini, E.; Giunchedi, P. Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery. Pharmaceutics 2020, 12, 658.
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