ORAL DIAGNOSIS
Original Articles
CHITOSAN MODIFIED POLY ( LACTIC-CO-GLYCOLIC ) ACID NANOPARTICLES INTERACTION WITH NORMAL , PRECANCEROUS KERATINOCYTES AND DENTAL PULP CELLS
Maria Justina Roxana Virlan 1a , Bogdan Calenic 1b , Cimpan Mihaela Roxana 2c , Daniela Elena Costea 3d , Maria Greabu 1e *
¹ Department of Biochemistry , Faculty of Dentistry , University of Medicine and Pharmacy Carol Davila , Bucharest , Romania ² Department of Clinical Dentistry - Biomaterials , Faculty of Medicine and Dentistry , University of Bergen , Bergen , Norway
3
The Gade Laboratory of Pathology , Department of Clinical Medicine , University of Bergen , Bergen , Norway a
DDS , MSc , PhD Student b
DDS , PhD , Lecturer c
DDS , PhD , Associate Professor d
DDS , PhD , Professor e
PhD , Professor , Head of Department
Abstract
Received : February 28 , 2017 Revised : March 22 , 2017 Accepted : April 02 , 2017 Published : April 03 , 2017
Academic Editor : David Wray , MD ( Honours ), BDS , MB ChB , FDS , RCPS ( Glasgow ), FDS RCS ( Edinburgh ) F Med Sci Professor Em ., Professor , University of Glasgow , Glasgow , UK
Cite this article : Virlan MJR , Calenic B , Cimpan MR , Costea DE , Greabu M . Chitosan modified poly ( lactic-co-glycolic ) acid nanoparticles interaction with normal , precancerous keratinocytes and dental pulp cells . Stoma Edu J . 2017 ; 4 ( 1 ): 16-26 .
Introduction : Nanoparticles ( NPs ) can carry molecules to different body tissues . Due to their controlled delivery properties , chitosan covered poly-lacto-co-glycolic NPs ( PLGAChi NPs ) could be used to deliver drugs to oral tissues for the treatment of dental diseases or in anticancer therapy . The aim of this study was to determine the uptake and cytotoxicity of PLGAChi NPs on different types of cells found in the oral cavity . Methodology : Normal oral keratinocytes ( NOKs ), precancerous keratinocytes ( POE9i ) and dental pulp cells ( DPCs ) were exposed for 12h and 24h to 20 g / mL and 200 g / mL PLGAChi NPs covalently tagged with fluorescein . 3D organotypic tissues of oral mucosa were grown in vitro and exposed to 200g / mL PLGAChi NPs for 24h . Results : Both normal and premalignant oral mucosa cells ( NOKs and POE9i ) displayed uptake of PLGAChiNPs in a time and concentration-dependent manner , both in 2D and 3D models . A higher and more rapid uptake of PLGAChi NPs by precancerous cell line POE9i was observed when compared to NOKs . Interestingly , DPCs did not display internalized PLGAChi NPs , even at the highest concentration of 200 g / mL . Conclusion : Chitosan-coated PLGAChi NPs proved to be able to cross the cellular membrane of oral keratinocytes , in 2D as well as in 3D cultures . The polymeric NPs used in the present study seem not to be suitable for applications that require NPs uptake by DPCs , as no evidence of uptake in these cells was found in this study . The finding that PLGAChi NPs showed significant internalization by human keratinocytes indicate that they could be used for drug delivery purposes to oral mucosa . Keywords : chitosan , PLGAChi , nanoparticles , oral keratinocytes , dental pulp .
1 . Introduction Polymeric nanoparticles ( NPs ) have been considered as the most efficient vehicles for drug delivery due to their excellent pharmacokinetic properties such as particle size , surface charge , surface chemistry , hydrophobicity , degree of rigidity and degradation speed . 1-3 Specifically , poly-lacto-co-glycolic NPs ( PLGA NPs ) can transport molecules to different tissues in the body , facilitating intracellular uptake of various drugs . 4 However , the overall negative charge of PLGA NPs has been reported to diminish their interaction with the negatively charged cell membrane . 5-6 PLGA NPs can be surface modified to carry a positive charge by the addition of a chitosan shell . PLGA-chitosan NPs combine the positive charge of chitosan and PLGA ’ s ability to efficiently entrap hydrophobic and hydrophilic drugs . 7-8 Chitosan , the deacetylated derivative of chitin , is used as the coating polymer , because it is cationic , biocompatible and biodegradable . 28 Chitosanmodified NPs were develloped for the transport of active molecules through nasal , ocular , vaginal or intestinal mucosa . 6
* Corresponding author :
Prof . Dr . Maria Greabu , PhD , Professor , Department of Biochemistry , Faculty of Dentistry , „ Carol Davila ” University of Medicine and Pharmacy of Bucharest , Bucharest , Romania 8 Blvd . Eroii Sanitari , Sector 5 , RO-050474 Bucharest , Romania Tel / Fax : + 40.721.274.932 / + 40.213.110.984 , e-mail : mariagreabu @ yahoo . com
16 Stoma Edu J . 2017 ; 4 ( 1 ): 16-26 . http :// www . stomaeduj . com