Parası kalmadığı için otobüse binemiyordur ailesi porno izle ona daha yeni para gönderdiği için tekrar porno istemeye utanınca mecburen otostop çekmek için youporn çantasını alarak yol kenarına gelir etekli porno liseli türk kız yol kenarında dururken yanına yaklaşan porno kibar bir gencin onu gideceği yere kadar bırakmak porno izle istemesine çok mutlu olur arabaya bindiklerinde gideceği yer ile porno arabayı kullanan adamın gittiği yer arasında çok mesafe sex izle farkı olduğunu anlayan türk kız bu yaptığı porno indir iyilik karşısında arabada ona memelerini açar porno sapıklaşan adam yol kenarındaki hotelde durarak porno izle üniversiteli otostop çeken türk kızına odada sakso çektirip sikerLaser facilitates week-long sustained transdermal drug delivery at high doses| Abstract

Abstract

Laser facilitates week-long sustained transdermal drug delivery at high doses

Author(s): Xinyuan Chen

Traditional patches are most successful in transdermal delivery of low-dose hydrophobic drugs. Week-long transdermal delivery of high-dose hydrophilic drugs remains a big challenge. We recently developed a laser-based powder delivery platform to allow high-dose week-long sustained delivery of hydrophilic drugs across the skin. This platform is based on laser treatment to generate skin microchannels (MCs) followed by topical application of powder drug- coated reservoir patches. Water evaporated from skin MCs gradually dissolve topical drug powder to elicit week-long sustained drug delivery in murine models. Using sulforhodamine b, zidovudine, and bovine serum albumin as model hydrophilic drugs, we found tapped coating could coat 10-20 mg drug per 0.5 cm2 reservoir patch to elicit 3-day sustained delivery, while compression coating could coat ~35-70 mg drug per 0.5 cm2 reservoir patch to elicit week-long sustained delivery. Besides sustained drug delivery, laser-assisted powder reservoir patch delivery also showed a good safety. Laser-generated skin MCs resealed in 1-2 days and completely recovered in 3 days after the week-long sustained delivery. AFL-assisted powder reservoir patch delivery involves no complex powder formulation and only requires incorporation of highly water-soluble mannitol or a similar excipient to elicit the high-efficient delivery. Enlarging reservoir patch size to 10 cm2 can conveniently expands the delivery capacity to gram scale. To our knowledge, this is the first time that high-dose week-long sustained transdermal delivery of hydrophilic drugs was achieved via a simple laser-based powder delivery platform.


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