Immunomodulatory Effect of Novel Electrospun Nanofibers Loaded with Doxycycline As an Adjuvant Treatment in Periodontitis

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2023 Feb 25

PMID 36840029

Authors

Vlad Andrei

Sanda Andrei

Adrian Florin Gal

Vasile Rus

Luciana-Madalina Gherman

Bianca Adina Bosca

Mihaela Niculae

Reka Barabas

Oana Cadar

Elena Dinte

Dana-Maria Muntean

Cosmin Petru Pestean

Horatiu Rotar

Antonia Boca

Andreea Chis

Manuela Taut

Sebastian Candrea

Aranka Ilea

Affiliations

Soon will be listed here.

Abstract

The immunomodulatory effect of a novel biomaterial obtained through electrospinning, based on polylactic acid (PLA) and nano-hydroxyapatite (nano-HAP), loaded with doxycycline (doxy) was evaluated in an animal model. The treatment capabilities as a local non-surgical treatment of periodontitis was investigated on the lower incisors of Wistar rats, after the induction of localized periodontitis using the ligature technique. Following the induction of the disease, the non-surgical treatment of scaling and root planing was applied, in conjunction with the application of the new material. The results of the treatment were evaluated clinically, using the tooth mobility and gingival index scores, as well as histologically. The salivary concentrations of matrix metalloproteinase 8 (MMP-8) and plasmatic concentrations of interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also monitored. Two weeks after the ligature application, the periodontal disease was successfully induced in rats. The application of the novel biomaterial obtained through electrospinning was proven to be more effective in improving the clinical parameters, while decreasing the salivary MMP-8 and plasmatic IL-1 and TNF-α concentrations, compared to the simple scaling and root planing. Thus, the novel electrospun biomaterial could be a strong candidate as an adjuvant to the non-surgical periodontal therapy.

Citing Articles

Local Drug Delivery Systems as Novel Approach for Controlling NETosis in Periodontitis.

Bosca A, Dinte E, Mihu C, Parvu A, Melincovici C, Sovrea A Pharmaceutics. 2024; 16(9).

PMID: 39339210 PMC: 11435281. DOI: 10.3390/pharmaceutics16091175.

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives.

Huang J, Yan Z, Song Y, Chen T Pharmaceutics. 2024; 16(5).

PMID: 38794313 PMC: 11125447. DOI: 10.3390/pharmaceutics16050651.

Biomaterials Functionalized with Inflammasome Inhibitors-Premises and Perspectives.

Vinteler N, Feurdean C, Petkes R, Barabas R, Bosca B, Muntean A J Funct Biomater. 2024; 15(2).

PMID: 38391885 PMC: 10889089. DOI: 10.3390/jfb15020032.

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

Jain P, Aamir Mirza M, Reyaz E, Beg M, Selvapandiyan A, Hasan N ACS Omega. 2024; 9(4):4455-4465.

PMID: 38313517 PMC: 10831838. DOI: 10.1021/acsomega.3c07092.

Are Local Drug Delivery Systems a Challenge in Clinical Periodontology?.

Budala D, Luchian I, Tatarciuc M, Butnaru O, Armencia A, Virvescu D J Clin Med. 2023; 12(12).

PMID: 37373830 PMC: 10298898. DOI: 10.3390/jcm12124137.

References

Tomina D, Petrutiu S, Dinu C, Crisan B, Cighi V, Ratiu I . Comparative Testing of Two Ligature-Induced Periodontitis Models in Rats: A Clinical, Histological and Biochemical Study. Biology (Basel). 2022; 11(5). PMC: 9137742. DOI: 10.3390/biology11050634. View

Chen D, Zhong L, Li Y, He R, Ding C, Chen X . Changes in serum inflammatory factor interleukin-6 levels and pathology of carotid vessel walls of rats with chronic periodontitis and diabetes mellitus after the periodontal intervention. Saudi J Biol Sci. 2020; 27(6):1679-1684. PMC: 7254042. DOI: 10.1016/j.sjbs.2020.04.029. View

Xu Y, Wei W . A comparative study of systemic subantimicrobial and topical treatment of minocycline in experimental periodontitis of rats. Arch Oral Biol. 2006; 51(9):794-803. DOI: 10.1016/j.archoralbio.2006.03.018. View

Emingil G, Atilla G, Sorsa T, Savolainen P, Baylas H . Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic periodontitis. J Periodontol. 2004; 75(10):1387-96. DOI: 10.1902/jop.2004.75.10.1387. View

Jepsen K, Jepsen S . Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 2000. 2016; 71(1):82-112. DOI: 10.1111/prd.12121. View

Graves D, Cochran D . The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003; 74(3):391-401. DOI: 10.1902/jop.2003.74.3.391. View

Andrei V, Fit N, Matei I, Barabas R, Bizo L, Cadar O . In Vitro Antimicrobial Effect of Novel Electrospun Polylactic Acid/Hydroxyapatite Nanofibres Loaded with Doxycycline. Materials (Basel). 2022; 15(18). PMC: 9502851. DOI: 10.3390/ma15186225. View

Van Doren S . Matrix metalloproteinase interactions with collagen and elastin. Matrix Biol. 2015; 44-46:224-31. PMC: 4466143. DOI: 10.1016/j.matbio.2015.01.005. View

Graziani F, Karapetsa D, Alonso B, Herrera D . Nonsurgical and surgical treatment of periodontitis: how many options for one disease?. Periodontol 2000. 2017; 75(1):152-188. DOI: 10.1111/prd.12201. View

10.

Luchian I, Goriuc A, Sandu D, Covasa M . The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int J Mol Sci. 2022; 23(3). PMC: 8837018. DOI: 10.3390/ijms23031806. View

11.

Ilea A, Andrei V, Feurdean C, Babtan A, Petrescu N, Campian R . Saliva, a Magic Biofluid Available for Multilevel Assessment and a Mirror of General Health-A Systematic Review. Biosensors (Basel). 2019; 9(1). PMC: 6468816. DOI: 10.3390/bios9010027. View

12.

Singhvi M, Zinjarde S, Gokhale D . Polylactic acid: synthesis and biomedical applications. J Appl Microbiol. 2019; 127(6):1612-1626. DOI: 10.1111/jam.14290. View

13.

Di Cristo F, Valentino A, De Luca I, Peluso G, Bonadies I, Calarco A . PLA Nanofibers for Microenvironmental-Responsive Quercetin Release in Local Periodontal Treatment. Molecules. 2022; 27(7). PMC: 9000246. DOI: 10.3390/molecules27072205. View

14.

Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T . Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol. 2020; 47 Suppl 22:4-60. PMC: 7891343. DOI: 10.1111/jcpe.13290. View

15.

Gad H, Kamel A, Ezzat O, El Dessouky H, Sammour O . Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development, in-vitro and in-vivo clinical evaluation. Expert Opin Drug Deliv. 2017; 14(11):1241-1251. DOI: 10.1080/17425247.2017.1329297. View

16.

Ortiz-Sanchez B, Legorreta-Herrera M, Rodriguez-Sosa M . Influence of Gestational Hormones on the Bacteria-Induced Cytokine Response in Periodontitis. Mediators Inflamm. 2021; 2021:5834608. PMC: 8545568. DOI: 10.1155/2021/5834608. View

17.

Oz H, Puleo D . Animal models for periodontal disease. J Biomed Biotechnol. 2011; 2011:754857. PMC: 3038839. DOI: 10.1155/2011/754857. View

18.

Papapanou P, Sanz M, Buduneli N, Dietrich T, Feres M, Fine D . Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018; 89 Suppl 1:S173-S182. DOI: 10.1002/JPER.17-0721. View

19.

Yun J, Lee J, Ha C, Park S, Kim S, Koo K . The effect of 3-D printed polylactic acid scaffold with and without hyaluronic acid on bone regeneration. J Periodontol. 2021; 93(7):1072-1082. DOI: 10.1002/JPER.21-0428. View

20.

Cafiero C, Spagnuolo G, Marenzi G, Martuscelli R, Colamaio M, Leuci S . Predictive Periodontitis: The Most Promising Salivary Biomarkers for Early Diagnosis of Periodontitis. J Clin Med. 2021; 10(7). PMC: 8038382. DOI: 10.3390/jcm10071488. View