Pimecrolimus

Pimecrolimus enhanced the expression of antimicrobial peptides cathelicidin and human beta-defensin-2 and beta-defensin-3 in human keratinocytes stimulated with Toll-like receptor 2/6 ligands. The drug also increased CD14 expression and enhanced the functional capacity of keratinocytes to inhibit the growth of Staphylococcus aureus. Pimecrolimus decreased TLR2/6-induced expression of IL-10 and IL-1 beta and inhibited nuclear translocation of both NFAT and NF-kappaB in keratinocytes.
These findings revealed a previously unreported function for pimecrolimus in cutaneous innate host defense, demonstrating that topical calcineurin inhibitors may enhance innate immune responses while suppressing adaptive immune responses. The mechanism involves binding to FKBP-12, inhibiting calcineurin phosphatase activity, and blocking NFAT dephosphorylation, which prevents NFAT nuclear translocation and subsequent transcription of pro-inflammatory cytokine genes.

Fig. 1 Pimecrolimus suppresses NFAT and NF-jB nuclear translocation in human keratinocytes. (Büchau A S.; et al. 2008)

Pimecrolimus nanoemulsion was developed using a high-energy ultrasonication technique with Tween 80 as surfactant, ethanol as co-surfactant, and benzyl alcohol as the oil phase. The optimized formulation exhibited a droplet size of 45.1 nm, entrapment efficiency of 92.59 percent, and polydispersity index of 0.402. In vitro release studies demonstrated that the nanoemulsion released 76.3 percent of pimecrolimus within 5 hours and 96.6 percent within 24 hours, compared to only 42.5 percent release from the commercial cream over the same period. This nanoemulsion formulation represents a promising nanocarrier approach for enhancing the solubility and skin permeability of hydrophobic pimecrolimus for topical delivery.

Fig. 2 Drug release profile of pimecrolimus from the prepared nanoemulsion formulas in comparison to pimecrolimus commercial pmc cream. (Challoob S A, Maraie N K. 2025)