Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Drug Delivery Assessment of a Novel Triple Antibiotic-Eluting Injectable Platelet-Rich Fibrin Scaffold: An In Vitro Study

Author(s): Azade Rafiee, Mahtab Memarpour, Sara Taghvamanesh, Forough Karami, Somayeh Karami and Mohammad H. Morowvat*

Volume 22, Issue 3, 2021

Published on: 05 June, 2020

Page: [380 - 388] Pages: 9

DOI: 10.2174/1389201021666200605110250

Price: $65

Abstract

Background: Intracanal disinfection is a critical, yet challenging goal for long-term success in regenerative-based treatments. This in-vitro study aimed to assess the release profile of triple antibiotic- eluting Injectable Platelet-Rich Fibrin (I-PRF) constructs in 28 days.

Methods: I-PRF scaffolds containing triple antibiotic mixture [Metronidazole (MET), Ciprofloxacin (CIP), and Minocycline (MINO)] by immersion (group one), I-PRF scaffolds containing triple antibiotic mixture by integration (group two), and antibiotic-free I-PRF scaffolds (group three) were fabricated. The antibiotic release from the scaffolds was measured using High-Performance Liquid Chromatography (HPLC) (the mobile phase of 0.1% formic acid and methanol (35:65 v/v), a C18 analytical column (150 × 4.6 mm, 5 μm) at a flow rate of 0.7 mL/min, at 25ºC) at days 1, 3, 7, 14, 21, and 28.

Results: Retention times for MINO, CIP, and MET were achieved as 2.3, 2.6, and 3.1 min, respectively. The maximum UV absorbance values for CIP, MET, and MINO were 268 nm, 278 nm, and 350 nm, respectively. The results of the first group showed burst release within the first 24 hours followed by sustained maintenance of all three antibiotics up to 14 days. MINO and MET were still detectable in the third week. The second group could not sustainably release the antibiotics.

Conclusion: The developed method for the simultaneous identification and quantification of each antibiotic in I-PRF was sensitive and quick. Overall, group one could take up the antibiotics in adequate quantities and then subsequently release them over the study period.

Keywords: Antibiotic, regeneration, scaffold, sustained drug delivery, retention times, tissue engineering.

Graphical Abstract
[1]
Albuquerque, M.T.P.; Valera, M.C.; Nakashima, M.; Nör, J.E.; Bottino, M.C. Tissue-engineering-based strategies for regenerative endodontics. J. Dent. Res., 2014, 93(12), 1222-1231.
[http://dx.doi.org/10.1177/0022034514549809] [PMID: 25201917]
[2]
Louwakul, P.; Saelo, A.; Khemaleelakul, S. Efficacy of calcium oxide and calcium hydroxide nanoparticles on the elimination of Enterococcus faecalis in human root dentin. Clin. Oral Investig., 2017, 21(3), 865-871.
[http://dx.doi.org/10.1007/s00784-016-1836-x] [PMID: 27129586]
[3]
Soares, J.A.; Roque de Carvalho, M.A.; Cunha Santos, S.M.; Mendonça, R.M.; Ribeiro-Sobrinho, A.P.; Brito-Júnior, M.; Magalhães, P.P.; Santos, M.H.; de Macêdo Farias, L. Effectiveness of chemomechanical preparation with alternating use of sodium hypochlorite and EDTA in eliminating intracanal Enterococcus faecalis biofilm. J. Endod., 2010, 36(5), 894-898.
[http://dx.doi.org/10.1016/j.joen.2010.01.002] [PMID: 20416441]
[4]
Shrestha, A.; Kishen, A. Antibacterial nanoparticles in endodontics: A review. J. Endod., 2016, 42(10), 1417-1426.
[http://dx.doi.org/10.1016/j.joen.2016.05.021] [PMID: 27520408]
[5]
Alves, F.R.F.; Andrade-Junior, C.V.; Marceliano-Alves, M.F.; Pérez, A.R.; Rôças, I.N.; Versiani, M.A.; Sousa-Neto, M.D.; Provenzano, J.C.; Siqueira, J.F., Jr Adjunctive steps for disinfection of the mandibular molar root canal system: A correlative bacteriologic, micro-computed tomography, and cryopulverization approach. J. Endod., 2016, 42(11), 1667-1672.
[http://dx.doi.org/10.1016/j.joen.2016.08.003] [PMID: 27641947]
[6]
Albuquerque, M.T.P.; Nagata, J.Y.; Diogenes, A.R. Clinical perspective of electrospun nanofibers as a drug delivery strategy for regenerative endodontics. Curr. Oral Health Rep., 2016, 3, 209-220.
[http://dx.doi.org/10.1007/s40496-016-0103-1]
[7]
Topçuoğlu, H.S.; Aktı, A.; Topçuoğlu, G.; Düzgün, S.; Ulusan, Ö.; Akpek, F. Effectiveness of conventional syringe irrigation, vibringe, and passive ultrasonic irrigation performed with different irrigation regimes in removing triple antibiotic paste from simulated root canal irregularities. J. Conserv. Dent., 2016, 19(4), 323-327.
[http://dx.doi.org/10.4103/0972-0707.186452] [PMID: 27563179]
[8]
Diogenes, A.; Ruparel, N.B.; Shiloah, Y.; Hargreaves, K.M. Regenerative endodontics: A way forward. J. Am. Dent. Assoc., 2016, 147(5), 372-380.
[http://dx.doi.org/10.1016/j.adaj.2016.01.009] [PMID: 27017182]
[9]
Kim, J.H.; Kim, Y.; Shin, S.J.; Park, J.W.; Jung, I.Y. Tooth discoloration of immature permanent incisor associated with triple antibiotic therapy: A case report. J. Endod., 2010, 36(6), 1086-1091.
[http://dx.doi.org/10.1016/j.joen.2010.03.031] [PMID: 20478471]
[10]
Bose, R.; Nummikoski, P.; Hargreaves, K. A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. J. Endod., 2009, 35(10), 1343-1349.
[http://dx.doi.org/10.1016/j.joen.2009.06.021] [PMID: 19801227]
[11]
Yadlapati, M.; Souza, L.C.; Dorn, S.; Garlet, G.P.; Letra, A.; Silva, R.M. Deleterious effect of triple antibiotic paste on human periodontal ligament fibroblasts. Int. Endod. J., 2014, 47(8), 769-775.
[http://dx.doi.org/10.1111/iej.12216] [PMID: 24246167]
[12]
Chuensombat, S.; Khemaleelakul, S.; Chattipakorn, S.; Srisuwan, T. Cytotoxic effects and antibacterial efficacy of a 3-antibiotic combination: An in vitro study. J. Endod., 2013, 39(6), 813-819.
[http://dx.doi.org/10.1016/j.joen.2012.11.041] [PMID: 23683284]
[13]
Ruparel, N.B.; Teixeira, F.B.; Ferraz, C.C.R.; Diogenes, A. Direct effect of intracanal medicaments on survival of stem cells of the apical papilla. J. Endod., 2012, 38(10), 1372-1375.
[http://dx.doi.org/10.1016/j.joen.2012.06.018] [PMID: 22980180]
[14]
Kamocki, K.; Nör, J.E.; Bottino, M.C. Dental pulp stem cell responses to novel antibiotic-containing scaffolds for regenerative endodontics. Int. Endod. J., 2015, 48(12), 1147-1156.
[http://dx.doi.org/10.1111/iej.12414] [PMID: 25425048]
[15]
Albuquerque, M.T.P.; Nagata, J.; Bottino, M.C. Antimicrobial efficacy of triple antibiotic-eluting polymer nanofibers against multispecies biofilm. J. Endod., 2017, 43(9S), S51-S56.
[http://dx.doi.org/10.1016/j.joen.2017.06.009] [PMID: 28778504]
[16]
Bottino, M.C.; Kamocki, K.; Yassen, G.H.; Platt, J.A.; Vail, M.M.; Ehrlich, Y.; Spolnik, K.J.; Gregory, R.L. Bioactive nanofibrous scaffolds for regenerative endodontics. J. Dent. Res., 2013, 92(11), 963-969.
[http://dx.doi.org/10.1177/0022034513505770] [PMID: 24056225]
[17]
Moradian, H.; Rafiee, A.; Ayatollahi, M. Design and fabrication of a novel transplant combined with human bone marrow mesenchymal stem cells and platelet-rich fibrin: New horizons for periodontal tissue regeneration after dental trauma. Iran. J. Pharm. Res., 2017, 16(4), 1370-1378.
[PMID: 29552046]
[18]
Kour, P.; Pudakalkatti, P.S.; Vas, A.M.; Das, S.; Padmanabhan, S. Comparative evaluation of antimicrobial efficacy of platelet-rich plasma, platelet-rich fibrin, and injectable platelet-rich fibrin on the standard strains of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Contemp. Clin. Dent., 2018, 9(Suppl. 2), S325-S330.
[http://dx.doi.org/10.4103/ccd.ccd_367_18] [PMID: 30294166]
[19]
Abd El Raouf, M.; Wang, X.; Miusi, S.; Chai, J. Mohamed AbdEl-Aal, A.B.; Nefissa Helmy, M.M.; Ghanaati, S.; Choukroun, J.; Choukroun, E.; Zhang, Y.; Miron, R.J. Injectable-platelet rich fibrin using the low speed centrifugation concept improves cartilage regeneration when compared to platelet-rich plasma. Platelets, 2019, 30(2), 213-221.
[http://dx.doi.org/10.1080/09537104.2017.1401058 PMID: 29240523]
[20]
Miron, R.J.; Fujioka-Kobayashi, M.; Hernandez, M.; Kandalam, U.; Zhang, Y.; Ghanaati, S.; Choukroun, J. Injectable platelet rich fibrin (i-PRF): Opportunities in regenerative dentistry? Clin. Oral Investig., 2017, 21(8), 2619-2627.
[http://dx.doi.org/10.1007/s00784-017-2063-9] [PMID: 28154995]
[21]
Varela, H.A.; Souza, J.C.M.; Nascimento, R.M. Injectable platelet rich fibrin: cell content, morphological, and protein characterization. Clin. Oral Investig., 2019, 23(3), 1309-1318.
[PMID: 30003342]
[22]
Dorj, B.; Won, J.E.; Purevdorj, O.; Patel, K.D.; Kim, J.H.; Lee, E.J.; Kim, H.W. A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery. Acta Biomater., 2014, 10(3), 1238-1250.
[http://dx.doi.org/10.1016/j.actbio.2013.11.002] [PMID: 24239677]
[23]
Albuquerque, M.T.; Ryan, S.J.; Münchow, E.A.; Kamocka, M.M.; Gregory, R.L.; Valera, M.C.; Bottino, M.C. Antimicrobial effects of novel triple antibiotic paste-mimic scaffolds on Actinomyces naeslundii biofilm. J. Endod., 2015, 41(8), 1337-1343.
[http://dx.doi.org/10.1016/j.joen.2015.03.005] [PMID: 25917945]
[24]
Albuquerque, M.T.; Valera, M.C.; Moreira, C.S.; Bresciani, E.; de Melo, R.M.; Bottino, M.C. Effects of ciprofloxacin-containing scaffolds on Enterococcus faecalis biofilms. J. Endod., 2015, 41(5), 710-714.
[http://dx.doi.org/10.1016/j.joen.2014.12.025] [PMID: 25698261]
[25]
Jasmine, S.; Thangavelua, A.; Janarthanan, K.; Krishnamoorthy, R.; Alshatwi, A.A. Antimicrobial and antibiofilm potential of injectable platelet rich fibrin-a second-generation platelet concentrate-against biofilm producing oral Staphylococcus isolates. Saudi J. Biol. Sci., 2020, 27(1), 41-46.
[http://dx.doi.org/10.1016/j.sjbs.2019.04.012] [PMID: 31889815]
[26]
Passos, P.C.; Moro, J.; Barcelos, R.C.S.; Da Rosa, H.Z.; Vey, L.T.; Bürguer, M.E.; Maciel, R.M.; Danesi, C.C.; Edwards, P.C.; Bottino, M.C.; Kantorski, K.Z. Nanofibrous antibiotic-eluting matrices: Biocompatibility studies in a rat model. J. Biomed. Mater. Res. B Appl. Biomater., 2020, 108(2), 306-315.
[http://dx.doi.org/10.1002/jbm.b.34389] [PMID: 31016876]
[27]
Wrightson, W.R.; Myers, S.R.; Galandiuk, S. Analysis of minocycline by high-performance liquid chromatography in tissue and serum. J. Chromatogr. B Biomed. Sci. Appl., 1998, 706(2), 358-361.
[http://dx.doi.org/10.1016/S0378-4347(97)00647-6] [PMID: 9551825]
[28]
Hargreaves, K.M.; Diogenes, A.; Teixeira, F.B. Treatment options: biological basis of regenerative endodontic procedures. J. Endod., 2013, 39(3)(Suppl.), S30-S43.
[http://dx.doi.org/10.1016/j.joen.2012.11.025] [PMID: 23439043]
[29]
Tanase, S.; Tsuchiya, H.; Yao, J.; Ohmoto, S.; Takagi, N.; Yoshida, S. Reversed-phase ion-pair chromatographic analysis of tetracycline antibiotics. Application to discolored teeth. J. Chromatogr. B Biomed. Sci. Appl., 1998, 706(2), 279-285.
[http://dx.doi.org/10.1016/S0378-4347(97)00563-X PMID: 9551814]
[30]
Sabrah, A.H.; Yassen, G.H.; Gregory, R.L. Effectiveness of antibiotic medicaments against biofilm formation of Enterococcus faecalis and Porphyromonas gingivalis. J. Endod., 2013, 39(11), 1385-1389.
[http://dx.doi.org/10.1016/j.joen.2013.05.003] [PMID: 24139259]
[31]
Zeng, Q.; Nguyen, S.; Zhang, H.; Chebrolu, H.P.; Alzebdeh, D.; Badi, M.A.; Kim, J.R.; Ling, J.; Yang, M. Release of growth factors into root canal by irrigations in regenerative endodontics. J. Endod., 2016, 42(12), 1760-1766.
[http://dx.doi.org/10.1016/j.joen.2016.04.029] [PMID: 27871480]
[32]
Howard, C.; Murray, P.E.; Namerow, K.N. Dental pulp stem cell migration. J. Endod., 2010, 36(12), 1963-1966.
[http://dx.doi.org/10.1016/j.joen.2010.08.046] [PMID: 21092813]
[33]
Bansal, R.; Jain, A.; Mittal, S. Current overview on challenges in regenerative endodontics. J. Conserv. Dent., 2015, 18(1), 1-6.
[http://dx.doi.org/10.4103/0972-0707.148861] [PMID: 25657518]
[34]
Gao, J.; Huang, G.; Liu, G.; Liu, Y.; Chen, Q.; Ren, L.; Chen, C.; Ding, Z. A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects. J. Biomater. Appl., 2016, 31(2), 241-249.
[http://dx.doi.org/10.1177/0885328216654424] [PMID: 27288462]
[35]
Annonymus. American Association of Endodontists. Clinical considerations for a regenerative procedure. Am. Assoc. Endod., 2018. Revised 4-1-18

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy