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Innovative coenzyme Q10-loaded nanoformulation as an adjunct approach for the management of moderate periodontitis: preparation, evaluation, and clinical study

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Abstract

Periodontal diseases are worldwide chronic inflammatory conditions that are associated with heavy production of reactive oxygen species followed by damage of the tooth-supporting tissues. Although the mechanical approach of scaling and root planing (SRP) for removing of plaque is considered as the key element for controlling periodontitis, the anatomical complexity of the teeth hinders accessibility to deeper points. The aim of this study was to design a micellar nanocarrier of coenzyme Q10 (Q10) to support the management of moderate periodontitis. Q10 was formulated in nanomicelles (NMQ10) and evaluated regarding encapsulation efficiency, loading efficiency, percent yield, hydrodynamic size (Dh), polydispersity index (PDI), and zeta potential (ζ potential). NMQ10 was incorporated to in situ gelling systems and the in vitro release of Q10 was studied. A clinical study including evaluation of periodontal parameters and biochemical assay of total antioxidant capacity (T-AOC) and lipid peroxide was achieved. Results revealed that Q10 was efficiently entrapped in spherical-shaped stable NMQ10 with Dh, PDI, and ζ potential of 154.0 nm, 0.108, and − 31.67 mV, respectively. The clinical study revealed that SRP only exhibited improvement of the periodontal parameters. Also, assay of T-AOC and lipid peroxide revealed that their values diminished by 21.5 and 23.8%, respectively. On the other hand, SRP combined with local application of NMQ10 resulted in a significant management of the periodontal parameters, and likewise, the assayed biomarkers proved enhanced antioxidant activity over SRP alone. In conclusion, NMQ10 can be suggested as a promising nanosystem as an approach to support the management of chronic periodontitis. Such results could be used to conduct larger clinical studies.

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Abbreviations

% LQ10 :

Percent coenzyme Q10 leaked out of the NMQ10

% RQ10 :

% Retention of coenzyme Q10

API:

Active pharmaceutical ingredient

BOP:

Bleeding on probing

CAL:

Clinical attachment level

CGMP:

Current good manufacturing practices

CMC:

Critical micelle concentration

CP:

Carbopol 934

CTM:

Clinical trial material

DDS:

Drug delivery system

D h :

Hydrodynamic size

DIW:

Deionized water

EE%:

Encapsulation efficiency

EtQ10 :

Ethanolic solution of coenzyme Q10

FNM :

NMQ10 dispersion

FQ10 :

Coenzyme Q10 dispersion

FRs:

Free radicals

FT-IR:

Fourier-transform infrared spectroscopy

GCF:

Gingival crevicular fluid

GI:

Gingival index

GLP:

Good laboratory practices

HLB:

Hydrophilic–lipophilic balance

HPMC:

Hydroxypropyl methyl cellulose K4M

K407 :

Kolliphor® P 407

K–P:

Korsmeyer–Peppas

LE%:

Loading efficiency

LPO:

Lipid peroxidation

MC:

Methyl cellulose

MDA:

Malondialdehyde

NMP :

Coenzyme Q10-free nanomicelles

NMQ10 :

Coenzyme Q10-loaded nanomicelles

NMs:

Polymeric nanomicelles

NLCs:

Nanostructured lipid carriers

PB6.8 :

Phosphate buffer pH 6.8

PDI:

Polydispersity index

PDPs:

Periodontal pockets

PEO:

Polyethylene oxide

PI:

Plaque index

PPD:

Probing pocket depth

PPO:

Polypropylene oxide

Q10 :

Coenzyme Q10

ROS:

Reactive oxygen species

SRP:

Scaling and root planing

T-AOC:

Total antioxidant capacity

TBA:

Thiobarbituric acid

TEA:

Triethanolamine

TEM:

Transmission electron microscopy

Y%:

Percent yield

ζ potential:

Zeta potential

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Acknowledgments

We gratefully acknowledge Dr. Mohammad El Nabalawy, lecturer at the Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, for his support in the biochemical assay.

Author information

Authors and Affiliations

  1. Ministry of Health, Mansoura, Egypt

    Mohamed A. Shaheen

  2. Department of Oral Medicine and Periodontology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt

    Samah H. Elmeadawy & Mohamed M. Anees

  3. Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Fagr B. Bazeed

  4. Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Gomhoreyah St., Mansoura, 35516, Egypt

    Noha M. Saleh

Authors
  1. Mohamed A. Shaheen
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  2. Samah H. Elmeadawy
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  3. Fagr B. Bazeed
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  4. Mohamed M. Anees
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  5. Noha M. Saleh
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Contributions

Conceptualization: SHE, MMA, and FBB; methodology: MAS and NMS; formal analysis and investigation: MAS and NMS; writing—original draft preparation: NMS; writing—review and editing: SHE, MMA, and NMS; supervision: SHE, MMA, and FBB.

Corresponding author

Correspondence to Noha M. Saleh.

Ethics declarations

The experiments comply with the current laws of the country in which they were performed. All procedures were conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consents were obtained from all patients for being included in the study.

Competing interests

The authors declare that they have no competing interests.

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Shaheen, M.A., Elmeadawy, S.H., Bazeed, F.B. et al. Innovative coenzyme Q10-loaded nanoformulation as an adjunct approach for the management of moderate periodontitis: preparation, evaluation, and clinical study. Drug Deliv. and Transl. Res. 10, 548–564 (2020). https://doi.org/10.1007/s13346-019-00698-z

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