Category: Formulation and Quality
Purpose: The current study is emphasized on development of nanoemulsion loaded gel i.e. nanogel employing kalonji oil as a functional excipient for encapsulating tacrolimus and thereby affording synergistic anti-psoriatic efficacy.
Methods: The nanoemulsion prepared by spontaneous emulsification method was characterized for various quality attributes like globule size distribution and morphology. Further, nanogel was prepared by loading nanoemulsion into a gel base constituting 1.5 % w/v Carbopol 980 (pH 6.8), which is close to skin pH and thus of low irritation potential. The nanogel was evaluated for spreadability, viscosity, dermal bioavailability, and in vitro efficacy in A-431 cell line. In vivo performance was evaluated on psoriasis model in BALB/c mice by monitoring the parameters like ear thickness, spleen dimension and weight, levels of interleukins (TNF-α, IL-6) and psoriatic scoring. Furthermore, the clinical efficacy was also evaluated in psoriasis patients by monitoring the inflammation and redness associated with the condition.
Results: The developed nanoemulsion exhibited average-droplet size of 93.37±2.58 nm with polydispersity index of 0.330 ± 0.025 indicating uniform and homogenous distribution. The incorporation of nanoemulsion into gel improved the applicability of the formulation and, the properties of gel remained unaltered. The nanogel exhibited desirable spreadability with sustained release pattern (biphasic). In A-431 cell lines the nanoemulsion showed an increased growth inhibition as compared to free drug, which was attributed to the enhanced penetration effect and higher cellular uptake. Further, it was evident from the dermatokinetic study that the penetration of the nanogel was better and followed paracellular and transcellular pathways for skin permeation. Similarly, in case of permeation a 2.88- and 4.33-fold appreciation was observed in the case of viable layer for nanoemulsion and nanogel, respectively. Also, a significant reduction in serum cytokines and improvement in psoriatic condition was achieved in vivo, indicating nanogel formulation efficacy compared with marketed formulation (Tacroz Forte, Glenmark Pharmaceuticals Ltd, Maharashtra, India). Finally, the nanogel showed modest clinical efficacy when evaluated in psoriasis patients. The inflammation and redness associated with psoriasis was alleviated significantly in patients treated with nanogel.
Conclusion: The proposed formulation strategy of employing functional excipients with inherent anti-psoriatic activity prove to be efficacious and safe alternative with improved patient compliance and clinical benefit in psoriasis. This impels for further exploration on functional excipient-based delivery systems for psoriasis management. This also opens up a new arena in the functional excipient-based delivery systems for better management of other topical diseases like atopic dermatitis, acne etc.