Transdermal application of diacerin loaded-terpene enriched invasomes: an approach to augment anti-edema and nociception inhibition activity

Abstract

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 2³ factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert^® software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple in-vitro studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the ex-vivo performance was evaluated through ex-vivo skin permeation and deposition. Finally, it was subjected to an array of in-vivo tests, namely Draize test, histopathology, In-vivo skin penetration, edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (−55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm²), nociception inhibition (77%) and In-vivo skin penetration (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm², 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.

Graphical Abstract

Keywords:

• Diacerein
• full factorial
• osteoarthritis
• invasomes
• terpene

Authors contribution

Conceptualization, S.A.; formal analysis, S.A., M.M.F., M.A.S. and D.E.; investigation, S.A., M.M.F., M.A.S. and D.E.; resources S.A., M.M.F., M.A.S. and D.E.; writing—original draft preparation, S.A., M.M.F.; writing—review and editing, M.M.F., M.A.S. and D.E.; supervision, S.A. All authors have read and agreed to the published version of the manuscript.

Ethics approval

All the ex-vivo and in-vivo tests were approved by Research Ethics Committee, Faculty of Pharmacy Cairo University (Approval no. PI 3375) which followed the 507 Guide for Care and Use of Laboratory Animals declared by the US National Institute of Health (NIH 508 Publication No. 85–23, revised 2011).

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability statement

All data generated or analyzed during this study are included in this manuscript.

Additional information

Funding

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