Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy

Donnelly, Ryan F.; Morrow, Desmond I. J.; McCarron, Paul A.; Woolfson, A. David; Morrissey, A.; Juzenas, Petras; Juzeniene, Asta; Iani, Vladimir; McCarthy, Helen; Moan, Johan Emelian

doi:10.1016/j.jconrel.2008.05.002

Cited by 156 publications

(100 citation statements)

References 46 publications

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“…In addition, pre-treatment with conventional erbium:YAG laser improved the anesthetic efficacy of topically applied lidocaine [18,21]. Donnelly et al [36] evaluated microneedle-mediated intradermal delivery of 5-ALA, which enhanced ALA delivery to superficial regions of excised porcine skin, but not to deeper skin layers. This finding supports the idea that pre-treated vertical channels facilitate the delivery of topical photosensitizers, but contrasts with our finding that AFR-laserinduced microchannels are capable of enhancing drug delivery to deep dermis.…”

Section: Discussionmentioning

confidence: 99%

Fractional CO₂ laser‐assisted drug delivery

et al. 2010

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Background and Objectives: Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO 2 laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug. Materials and Methods: Two Yorkshire swine were treated with single-hole CO 2 laser AFR and subsequent topical application of MAL (Metvix 1 , Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 mm. AFR was performed with a 10.6 mm wavelength prototype CO 2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. Results: AFR created cone-shaped channels of approximately 300 mm diameter and 1,850 mm depth that were surrounded by a 70 mm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 mm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 mm from the holes (1,000, 1,800 mm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR. Conclusions: Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications. Lasers Surg.

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Section: Discussionmentioning

confidence: 99%

Fractional CO₂ laser‐assisted drug delivery

et al. 2010

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“…Ongoing research continues to investigate whether modifications to the standard PpIX-induced PDT protocol can be made to increase efficacy. For example, the use of ALA esters with lower lipophilicty such as MAL and HAL, employment of penetration enhancers such as DMSO [29], iron chelation [30], micro-needle arrays [23], an oxygen pressure injection (OPI) device [22], altering light dosimetry parameters [31], modifying oxygen levels [32] and ablative fractional laser resurfacing (AFXL) [33].…”

Section: Discussionmentioning

confidence: 99%

“…DMSO [16] or glycolic acid [17]), iontophoresis [18], lesion surface preparation (e.g. gentle curettage [19] or tape-stripping [20]), elevating skin temperature [21], pressurized oxygen [22], micro-needle puncture [23], nanoemulsions [24] and needleless jet injection [25].…”

Section: Introductionmentioning

confidence: 99%

The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device

Blake

Campbell

Allen

et al. 2012

Journal of Photochemistry and Photobiology B: Biology

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“…Donnelly et al worked on microneedle-mediated intradermal delivery of 5-aminolevulinic acid and transdermal delivery of meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate using silicon microneedles. [81,82] Ashraf et al designed a microfluidic drug delivery device with an electronic module, sensor for blood pressure and flow, and drug delivery device as its main components. [26] The system automatically injected the desired drug dose through microneedles at a controlled rate on sensing an increase in blood pressure.…”

Section: Drugsmentioning

confidence: 99%

Microneedles: an emerging transdermal drug delivery system

Bariya

Gohel

Mehta

et al. 2012

Journal of Pharmacy and Pharmacology

360

207

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Objectives One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Key findings Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Summary Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.

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Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy

Cited by 156 publications

References 46 publications

Fractional CO₂ laser‐assisted drug delivery

Fractional CO₂ laser‐assisted drug delivery

The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device

Microneedles: an emerging transdermal drug delivery system

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Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy

Cited by 156 publications

References 46 publications

Fractional CO2 laser‐assisted drug delivery

Fractional CO2 laser‐assisted drug delivery

The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device

Microneedles: an emerging transdermal drug delivery system

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Fractional CO₂ laser‐assisted drug delivery

Fractional CO₂ laser‐assisted drug delivery