Dasatinib-Loaded Topical Nano-Emulgel for Rheumatoid Arthritis: Formulation Design and Optimization by QbD, In Vitro, Ex Vivo, and In Vivo Evaluation

The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization.

Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.

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Materials

Peceol, geleol, labrasol, capryol 90, and transcutol-P were received as generous gift samples from Gattefosse (Mumbai, India). Dialysis membrane with a molecular weight cut off 12,000–14,000 and membrane filters (0.22 μm) were purchased from Merck (India). All other laboratory chemicals were purchased from HiMedia (Mumbai, India).

Donthi, M.R.; Saha, R.N.; Singhvi, G.; Dubey, S.K. Dasatinib-Loaded Topical Nano-Emulgel for Rheumatoid Arthritis: Formulation Design and Optimization by QbD, In Vitro, Ex Vivo, and In Vivo Evaluation. Pharmaceutics 2023, 15, 736. https://doi.org/10.3390/pharmaceutics15030736