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