title: In vivo immunomodulatory, cumulative skin irritation, sensitization and effect of d-limonene on permeation of 6-mercaptopurine through transdermal drug delivery.
abstract: Using skin as a port for systemic drug administration, transdermal drug delivery has expanded greatly over the last two decades. Our aim was to formulate the single layer drug-in-adhesive transdermal patch for 6-mercaptopurine (6-MP). In vitro permeation study was carried out using modified Franz diffusion cell with and without of different concentration of d-limonene in human cadaver skin. In vivo immunomodulatory was carried out in mice, cumulative skin irritation, sensitization and patch adherence study was done in both mice and human subjects. 6-MP flux increased from 43+/-12.2 microg/cm2h (control) to 162.8+/-32.2 microg/cm2h (6% w/v d-limonene) data was significant (p<0.05), with decrease in the lag time to 35+/-9.3 min compared to control of 90 +/-15.3 min. In vivo immunomodulatory effect was shown in the Balb/c mice with 100 mumol/kg/body wt of animal for 5d (one dose/d) of d-limonene. WBC count of 13469 cells/mm peak was observed on 12th day, bone marrow cells of 26.3 x 10(6) cells/femur and alpha-esterase positive cells of 1259+/-328.4 cells/4000 bone marrow cells. Cumulative skin irritation, sensitisation and patch adherence in animals and human subjects showed no skin irritation and sensitization. Patch adhesion was greater than 90.0% respectively in both human subjects and mice. The percentage of human subjects with adhesive residue was significantly less with scores of zero. d-Limonene proved as good chemical enhancer by increasing in the skin permeability with shortened the lag time. It proved that therapeutic amount of 6-MP can be delivered through transdermal drug delivery.
authors: Al-Ameen College of Pharmacy, Near Lalbagh main gate, Hosur road, Bangalore-560 027, karnataka, India. nschandrashekar@gmail.com
authors: N S
authors: NS
authors: Chandrashekar
authors: Shobha Rani Rajeev
authors: SR
authors: Hiremath
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D053138:Cyclohexenes / Q000009:adverse effects / Q000494:pharmacology*; D015194:Diffusion Chambers, Culture; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D007509:Irritants / Q000494:pharmacology*; D000077222:Limonene; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects*; D013729:Terpenes / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D053138:Cyclohexenes; D007166:Immunosuppressive Agents; D007509:Irritants; D013729:Terpenes; D000077222:Limonene; D015122:Mercaptopurine