curcumin and lucifer-yellow

Curcumin (CRM) (CAS number 458-37-07), a naturally-occurring molecule, has diverse pharmacological actions. Recently our research group demonstrated that poor permeability also contributes to its poor oral bioavailability. A self nano-emulsifying drug delivery system (CRM SNEDDS) consisting of Labrasol, Gelucire 44/14, Vitamin E TPGS and PEG 400 was designed and provided 16 times improvement in oral bioavailability in rats, at a dose of 250 mg/kg body weight. Caco-2 cell transport studies were conducted for CRM SNEDDS and CRM in the presence of individual excipients, to determine the extent of improvement in permeability. Papp values for CRM, CRM SNEDDS and CRM in combination with 4 individual excipients were calculated. Transepithelial electrical resistance value was assessed to evaluate the cell morphology and the cellular tight junctions. Permeation of a transcellular marker, Lucifer Yellow was used as a marker to assess monolayer integrity. The tested excipient concentrations were found to be non-toxic to the cell monolayer in 2 h incubation. Results showed that the Papp increased 6.35 times for curcumin in CRM SNEDDS as compared to CRM. Individual excipients enhanced permeation from 1.97 to 6.35 times, with Labrasol showing the highest enhancement of 6.35 times.

Topics: Algorithms; Antineoplastic Agents, Phytogenic; Biological Availability; Biological Transport, Active; Caco-2 Cells; Cell Membrane Permeability; Cell Survival; Chemistry, Pharmaceutical; Curcumin; Cytochrome P-450 CYP3A; Electric Impedance; Excipients; Humans; Isoquinolines; Microscopy, Electron, Scanning; Tight Junctions

Curcumin, the dietary pigment responsible for the yellow color of curry, has been reported to be a potent inhibitor of tumor promotion in mouse epidermis. Since most tumor promoters inhibit cell-cell communication, we have examined the effect of curcumin on the reduction of gap junctional intercellular communication induced by the phorbol ester phorbol-12,13-dibutyrate (PDBu) in BALB/c 3T3 cells. Treatment of cells with 50 microM curcumin slightly inhibited the dye coupling evaluated by intercellular transfer of a fluorescent dye Lucifer Yellow CH; however, lower concentrations of curcumin did not affect the level of intercellular communication. Addition of 200 nM PDBu caused a rapid reduction of dye coupling, which was not altered by either pretreatment or simultaneous curcumin addition.

Topics: 3T3 Cells; Animals; Cell Communication; Curcumin; Dose-Response Relationship, Drug; Fluorescent Dyes; Isoquinolines; Kinetics; Mice; Mice, Inbred BALB C; Phorbol 12,13-Dibutyrate