Transdermal microconduits by microscission for drug delivery and sample acquisition

BACKGROUND: Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 μm diameter areas of human skin in vivo. METHODS: Microscissioning is achieved by a limited flux of accelerated gas: 25 μm inert particles passing through the aperture in a mask held against the stratum corneum. The particles scize (cut) tissue, which is removed by the gas flow with the sensation of a gentle stream of air against the skin. The resulting microconduit is fully open and may be between 50 and 200 μm deep. RESULTS: In vivo adult human tests show that microconduits reduce the electrical impedance between two ECG electrodes from approximately 4,000 Ω to 500 Ω. Drug delivery has been demonstrated in vivo by applying lidocaine to a microconduit from a cotton swab. Sharp point probing demonstrated full anaesthesia around the site within three minutes. Topical application without the microconduit required approximately 1.5 hours. Approximately 180 μm deep microconduits in vivo yielded blood sample volumes of several μl, with a faint pricking sensation as blood enters tissue. Blood glucose measurements were taken with two commercial monitoring systems. Microconduits are invisible to the unaided eye, developing a slight erythematous macule that disappears over days. CONCLUSION: Microscissioned microconduits may provide a minimally invasive basis for delivery of any size molecule, and for extraction of interstitial fluid and blood samples. Such microconduits reduce through-skin electrical impedance, have controllable diameter and depth, are fully open and, after healing, no foreign bodies were visible using through-skin confocal microscopy. In subjects to date, microscissioning is painless and rapid

Akutna toksičnost veterinarskih i poljoprivrednih formulacija organofosfata diklorvosa i diazinona u pilića

Formulation components of organophosphate insecticidal preparations might affect their toxic action in animals. The objective of this study was to examine and compare the acute toxicity and cholinesterase inhibition in seven to 14-day-old chicks dosed orally with dichlorvos and diazinon in standard veterinary and agricultural formulations. The acute (24 h) oral median lethal doses (LD50) of the formulations were determined using the up-and-down method. Respective LD50 of dichlorvos of the veterinary and agricultural formulations in chicks were 11.1 mg kg-1 and 6.51 mg kg-1 and those of diazinon 6.4 mg kg-1 and 6.7 mg kg-1. Plasma and brain cholinesterase activities were measured by electrometry after in vivo and in vitro exposure to organophosphates. The chicks showed signs of cholinergic toxicosis within one hour of dosing. Dichlorvos (8 mg kg-1) and diazinon (4 mg kg-1) in the veterinary and agricultural formulation signifi cantly reduced both plasma and brain cholinesterase activities in the chicks. The veterinary formulation of dichlorvos reduced plasma ChE by 60 % and agricultural by 40 % and brain ChE by 93 % and 87 %, respectively. In contrast, ChE inhibition by diazinon in the agricultural formulation of diazinon was stronger than by the veterinary formulation; 72 % vs. 64 % in plasma and 97 % vs. 80 % in the brain, respectively. The highest in vitro inhibitions were observed with dichlorvos in the agricultural formulation (50 %) in the brain samples and with diazinon in the agricultural formulation (52 %) in the plasma samples. While they exist, differences between formulations cannot be taken as a rule and further investigations should inventory the toxicity of standard veterinary and agricultural organophosphate formulations in addition to the known data for pure forms.Sastojci formulacija mogu djelovati na toksičnost organofosfatnih insekticidnih pripravaka u životinja. Cilj je ovog istraživanja bio ispitati i usporediti akutnu inhibiciju kolinesteraza u pilića starih 7 do 14 dana koji su na usta primili organofosfatne insekticide diklorvos i diazinon u odgovarajućim formulacijama za veterinarsku odnosno poljoprivrednu primjenu. Dvadesetčetverosatna akutna letalna doza (LD50) diklorvosa bila je 11,1 mg kg-1 u veterinarskim odnosno 6,51 mg kg-1 u poljoprivrednim formulacijama, a diazinona 6,4 mg kg-1 odnosno 6,7 mg kg-1. Do kolinergičke toksikoze u pilića došlo je jedan sat nakon primjene. Nakon izlaganja organofosfatima in vivo i in vitro izmjerena je aktivnost kolinesteraza u plazmi i mozgu s pomoću elektrometrije. Oralne doze diklorvosa (8 mg kg-1) odnosno diazinona (4 mg kg-1) putem veterinarskih odnosno poljoprivrednih formulacija značajno su smanjile aktivnost kolinesteraza u plazmi i mozgu pilića. In vitro su također oba organofosfata inhibirala aktivnost kolinesteraza, bez obzira na formulaciju. Poljoprivredna formulacija diklorvosa izazvala je najjaču inhibiciju (50 %) u mozgu pilića, dok je poljoprivredna formulacija diazinona najjače inhibirala (52 %) aktivnost u plazmi. Ovo istraživanje pokazuje da različite formulacije organofosfatnih insekticida mogu dovesti do različita otrovanja i različito djelovati na kolinesteraznu aktivnost u mozgu i plazmi