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

Abstract

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. This study explored ablative fractional laser (AFL) to assist 3-day to week-long sustained transdermal delivery of powder hydrophilic drugs in murine models. Bulk drug powder was coated into reservoir patches followed by topical application onto AFL-treated skin. Water evaporated from AFL-generated skin microchannels (MCs) gradually dissolve topical drug powder to elicit multi-day sustained drug delivery. 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, AFL-assisted powder reservoir patch delivery showed a good safety. AFL-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 expand 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.