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

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

Sustained epidermal powder drug delivery via skin microchannels

Transdermal delivery of hydrophilic drugs is challenging. This study presents a novel sustained epidermal powder delivery technology (sEPD) for safe, efficient, and sustained delivery of hydrophilic drugs across the skin. sEPD is based on coating powder drugs into high-aspect-ratio, micro-coating channels (MCCs) followed by topical application of powder drug-coated array patches onto ablative fractional laser-generated skin MCs to deliver drugs into the skin. We found sEPD could efficiently deliver chemical drugs without excipients and biologics drugs in the presence of sugar excipients into the skin with a duration of ~ 12 h. Interestingly the sEPD significantly improved zidovudine bioavailability by ~ 100% as compared to oral gavage delivery. sEPD of insulin was found to maintain blood glucose levels in normal range for at least 6 h in chemical-induced diabetes mice, while subcutaneous injection failed to maintain blood glucose levels in normal range. sEPD of anti-programmed death-1 antibody showed more potent anti-tumor efficacy than intraperitoneal injection in B16F10 melanoma models. Tiny skin MCs and ‘bulk’ drug powder inside relatively deep MCCs are crucial to induce the sustained drug release. The improved bioavailability and functionality warrants further development of the novel sEPD for clinical use

Augmentation of vaccine-induced humoral and cellular immunity by a physical radiofrequency adjuvant

Vaccine adjuvants ensure sufficient engagement of the immune system in vaccination, however safety issues can be associated with novel chemical adjuvants. Here, Cao et al. report a physical radiofrequency adjuvant to simultaneously augment vaccine-induced humoral and cellular immune responses without potentially harmful adverse reactions