Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: statistical optimization and clinical assessment

Abstract

Atorvastatin calcium (ATV) is a well-known anti-hyperlipidemic drug currently being recognized for possessing an anti-inflammatory effect. Introducing it as a novel remedy for periodontitis treatment necessitates developing a syringeable modified delivery system capable of targeting inflammation within the periodontal pockets. Thus, a 3³ Box-Behnken design was used to generate eugenol enriched PEGylated cubosomes. Based on the desirability function, the optimized formulation (OEEPC) was selected exhibiting a solubilization efficiency (SE%) of 97.71 ± 0.49%, particle size (PS) of 135.20 ± 1.11 nm, polydispersity index (PDI) of 0.09 ± 0.006, zeta potential (ZP) of −28.30 ± 1.84 mV and showing a sustained drug release over 12 h. It displayed a cubic structure under the transmission electron microscope, furthermore, it was stable upon storage for up to 30 days. Hence, it was loaded into an optimum syringeable in-situ gel (ISG) which displayed the desired periodontal gelation temperature (34 ± 0.70 °C) and an adequate gelation time (46 ± 2.82 sec), it also released approximately 75% of the drug within 72 h. Clinical evaluation of the ISG showed a promising percentage reduction of about 58.33% in probing depth, 90% in the bleeding index, 81.81% in the plaque index, and 70.21% in gingival levels of transforming growth factor–β1. This proved that the formulated syringeable intra-pocket delivery system of ATV is an efficient candidate for diminishing inflammation in periodontitis.

Graphical Abstract

Keywords:

• Intra-pocket delivery
• periodontitis
• atorvastatin
• cubosomes
• Box-Behnken design
• and clinical assessment

Acknowledgements

The authors would like to thank Associate Professor Basant Ahmed Habib, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University for her help in the statistical analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.