title: Enhancement in deposition and permeation of 5-fluorouracil through human epidermis assisted by peptide dendrimers.
abstract: Enhancing the deposition and permeation of 5-fluorouracil across human epidermis assisted by appropriately charged and well-defined peptide dendrimers was investigated. Peptide dendrimers with arginine as the terminal amino acid and having a range of terminal positive charges (4(+), 8(+) and 16(+)) were synthesized by solid phase peptide synthesis. Various parameters including effect of peptide dendrimers on the solubility and partition coefficient of 5-FU, degradation of drug in skin as well as deposition and permeation of 5-FU in/through skin were studied. All the tested dendrimers increased the aqueous solubility and partition coefficient of 5-FU with each also significantly (p < 0.05) enhancing the deposition and permeation of 5-FU in/across human epidermis in a concentration-dependent manner. Of the three peptide dendrimers examined, R8 dendrimer (bearing 8(+) charge derived from four terminal arginines and MW of ≈1000 Da) showed greatest values for flux, Q(48) (cumulative amount of drug permeated at the end of 48 h) and amount of drug retained in human skin. Furthermore, this study also scrutinized and reports on the likely mechanisms by which peptide dendrimers act as transdermal permeation enhancers.
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal , Karnataka , India and.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Mutalik
authors.forename: Pallavi K
authors.initials: PK
authors.lastname: Shetty
authors.forename: Aravind
authors.initials: A
authors.lastname: Kumar
authors.forename: Rohit
authors.initials: R
authors.lastname: Kalra
authors.forename: Harendra S
authors.initials: HS
authors.lastname: Parekh
mesh_terms: D000279:Administration, Cutaneous; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D010455:Peptides / Q000737:chemistry*; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility
chemical_list: D000964:Antimetabolites, Antineoplastic; D050091:Dendrimers; D010455:Peptides; D005472:Fluorouracil