title: Skin permeation of D-limonene-based nanoemulsions as a transdermal carrier prepared by ultrasonic emulsification.
abstract: Nanoemulsions can be used for transporting pharmaceutical phytochemicals in skin-care products because of their stability and rapid permeation properties. However, droplet size may be a critical factor aiding permeation through skin and transdermal delivery efficiency. We prepared D-limonene nanoemulsions with various droplet sizes by ultrasonic emulsification using mixed surfactants of sorbitane trioleate and polyoxyethylene (20) oleyl ether under different hydrophilic-lipophilic balance (HLB) values. Droplet size decreased with increasing HLB value. With HLB 12, the droplet size was 23 nm, and the encapsulated ratio peaked at 92.3%. Transmission electron microscopy revealed spherical droplets and the gray parts were D-limonene precipitation incorporated in spherical droplets of the emulsion system. Franz diffusion cell was used to evaluate the permeation of D-limonene nanoemulsion through rat abdominal skin; the permeation rate depended on droplet size. The emulsion with the lowest droplet size (54 nm) achieved the maximum permeation rate. The concentration of D-limonene in the skin was 40.11 μL/cm(2) at the end of 360 min. Histopathology revealed no distinct voids or empty spaces in the epidermal region of permeated rat skin, so the D-limonene nanoemulsion may be a safe carrier for transdermal drug delivery.
authors.affiliation: Department of Medicinal Botanical and Health Applications, Da-Yeh University, No. 168, University Rd., Dacun, Changhua 51591, Taiwan, ROC.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Lu
authors.forename: Been-Huang
authors.initials: BH
authors.lastname: Chiang
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Huang
authors.forename: Po-Hsien
authors.initials: PH
authors.lastname: Li
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D053138:Cyclohexenes / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D057927:Hydrophobic and Hydrophilic Interactions; D000077222:Limonene; D049329:Nanostructures / Q000737:chemistry*; D010539:Permeability; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013729:Terpenes / Q000737:chemistry*; D014465:Ultrasonics
chemical_list: D053138:Cyclohexenes; D004337:Drug Carriers; D004655:Emulsions; D013729:Terpenes; D000077222:Limonene
keywords: Franz diffusion cell; Mixed surfactant; Nanoemulsions; Rat abdominal skin; Transdermal delivery; d-Limonene