Fractional laser‐assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration

Erlendsson, Andrés M.; Doukas, Apostolos G.; Farinelli, William A.; Bhayana, Brijesh; Anderson, R. Rox; Hædersdal, Merete

doi:10.1002/lsm.22374

Cited by 39 publications

(24 citation statements)

References 31 publications

(49 reference statements)

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“…Other techniques to enhance TDD include curettage, dermabrasion, iontophoresis, pressure waves, vacuum, and radiofrequency. Using these modalities, a myriad of medications have been successfully delivered transdermally, including triamcinolone, 5-aminolevulinic acid (5-ALA), 5-fluorouracil (5-FU), and methotrexate [5][6][7][8][9][10][11].…”

Section: Transdermal Drug Delivery (Tdd)mentioning

confidence: 99%

Challenges to laser‐assisted drug delivery: Applying theory to clinical practice

et al. 2017

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Background The percutaneous penetration of topically applied compounds can be enhanced using external chemical or physical sources and thus laser‐assisted drug delivery is a burgeoning area of interest within the field of dermatology. Objectives This article briefly discusses the mechanism of laser‐assisted drug delivery and expands upon the challenges and safety issues that may arise in the clinical implementation of this modality. Results The existing literature demonstrates that investigators and clinicians in dermatology have successfully delivered anti‐inflammatory, anti‐neoplastic, and anti‐oxidative medications transdermally for the treatment of a variety of conditions including scarring, photoageing, and cutaneous neoplasia. Despite growth of the field, much remains to be learned about the applicability of laser‐assisted drug delivery in humans, and practitioners are faced with new safety concerns that may be associated with this treatment modality. Conclusions Challenges in laser assisted drug delivery include unpredictability of dosing and response to therapy, possibility of inducing local and systemic reactions, and variability in treatment regimens. Lasers Surg. Med. 50:20–27, 2018. © 2017 Wiley Periodicals, Inc.

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Section: Transdermal Drug Delivery (Tdd)mentioning

confidence: 99%

Challenges to laser‐assisted drug delivery: Applying theory to clinical practice

et al. 2017

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“…Biphasic drug release is likely caused by differential powder dissolution in early and late phases. It was reported that interstitial fluid can quickly fill skin MCs after AFL treatment [34]. Patch application and firm pressing could bring lower portion of patch-coated drug powder in close contact with skin MC-filled interstitial fluid.…”

Section: Discussionmentioning

confidence: 99%

Sustained epidermal powder drug delivery via skin microchannels

Cao

Kakar

Hossen

et al. 2017

Journal of Controlled Release

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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 hours. 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 hours 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.

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“…To generate acoustic pressure waves the Legato II Impact (Alma Lasers Ltd., Nuremburg, Germany) was used at 70% energy intensity and 50 Hz acoustic pressure pulse rate for 12 seconds in an area of 3 × 3 cm. To generate pressure‐vacuum alterations a self‐made pressure‐vacuum‐pressure (PVP) device was used creating subsequent alternations in pressure for 3 minutes consisting of 1 minute relative positive pressure (atmospheric pressure + 1 bar), 1 minute relative negative pressure (atmospheric pressure − 0.7 bar), and relative 1 minute positive pressure (atmospheric pressure + 1 bar) based on an experimental device used by Erlendsson et al .…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, relatively long application times may be needed to reach optimal drug concentrations, limiting clinical feasibility in outpatient or day care based treatments like photodynamic therapy. Furthermore, AFXL channels are believed to be filled with interstitial fluid or even a fibrin plug already shortly after AFXL treatment, preventing uptake of topical drugs in the channels . In addition, in earlier clinical trials more deeply situated skin lesions such as nodular basal cell carcinomas have failed to respond to AFXL assisted photodynamic therapy, probably due to insufficient drug uptake in the deep dermis .…”

Section: Introductionmentioning

confidence: 99%

“…Various attempts have been made to increase and accelerate penetration of topical drugs through AFXL channels using physical penetration enhancement methods such as subsequent pressure vacuum alterations, transdermal acoustic pressure waves, and simple manual massage, with varying results . However, to date, no studies have been performed quantitatively investigating the spatial distribution of topical drugs in deeper skin layers after application of these enhancement techniques on AFXL pretreated skin.…”

Section: Introductionmentioning

confidence: 99%

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Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green

et al. 2019

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Background and Objectives Topical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL‐assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin. Materials and Methods In ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 μm, channel width 120 μm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography. Results FI was higher when using enhancement techniques compared to control (AFXL‐only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL‐only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3–24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL‐only were observed (P = 0.31). Conclusion Penetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL‐pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

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Fractional laser‐assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration

Abstract: Active filling with PVP secures filling of laser channels and induces a deeper, greater, more rapid delivery than conventional AFXL. This delivery technique has promise to improve treatment efficacy for medical treatments of dermally invasive lesions, such as BCCs.

Cited by 39 publications

References 31 publications

Challenges to laser‐assisted drug delivery: Applying theory to clinical practice

Challenges to laser‐assisted drug delivery: Applying theory to clinical practice

Sustained epidermal powder drug delivery via skin microchannels

Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green

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