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 weeklong sustained transdermal delivery of powder hydrophilic drugs in murine models. Bulk drug powder was coated into reservoir patches followed by topical application onto AFLtreated 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 cm 2 reservoir patch to elicit 3-day sustained delivery, while compression coating could coat ~35-70 mg drug per 0.5 cm 2 reservoir patch to elicit week-long sustained delivery. Besides sustained drug delivery, AFL-assisted powder reservoir patch delivery also showed a good safety. AFLgenerated 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 cm 2 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.

Vaccine delivery alerts innate immune systems for more immunogenic vaccination

“…Hair on the lateral dorsal skin of mice was removed 1 day before the experiment as in our previous report ( 52 ). For LPD, hair-removed skin was treated with AFL to generate a 6 × 6 array of skin MCs in 3 × 3 mm 2 followed by topical application of powder OVA or pdm09 vaccine–coated array patches.…”

Non-Invasive Vaccines: Challenges in Formulation and Vaccine Adjuvants

“…Laser ablation is a conventional technology used to remove the entire surface of the skin, whereas fractional laser creates micro-columns in the skin, leaving the surrounding areas intact to minimize skin damage and accelerate the healing process [ 239 ]. Ablative fractional laser (AFL) is a method that combines the laser ablation and fractional laser technologies, minimizing skin damage and enhancing vaccine permeability by ablating the stratum corneum and forming skin microchannels [ 240 ].…”

Recent Biomedical Approaches for Chitosan Based Materials as Drug Delivery Nanocarriers

“…TDDSs are non-invasive in comparison to parenteral administration, remaining relatively painless, therefore enhancing patient compliance and acceptability [ 152 ]. Nonetheless, there are various shortcomings of drug permeation due to the impermeability of the skin, especially due to the components from the structure of the stratum corneum, and as result only a small number of hydrophobic drugs, with molecular weight ≤500 Da, are able to penetrate via the transdermal administration [ 154 , 155 ]. For this reason, in order to enhance the ability of molecules to pass through the skin, many technologies have been developed and in the following we will give some examples of chitosan-based nanoformulations used as transdermal drug delivery systems.…”