Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections

Peng, Ke; Vora, Lalitkumar K.; Tekko, Ismaiel A.; Permana, Andi Dian; Domínguez-Robles, Juan; Ramadon, Delly; Chambers, Philip; McCarthy, Helen; Larrañeta, Eneko; Donnelly, Ryan F.

doi:10.1016/j.jconrel.2021.10.001

Cited by 65 publications

(38 citation statements)

References 114 publications

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“…MNs are microscopic projections that disrupt the top layer of the skin in a non-invasive manner, creating micron-sized channels ranging in height from 25 to 2000 µm that allow drugs to reach the epidermis or upper dermis directly [283,286,289]. MNs have facilitated the transdermal delivery of not only low-molecular weight drugs [290,291] but also hydrophilic molecules [292,293], peptides and proteins [294][295][296][297], cosmeceuticals [298][299][300], microparticles [301,302], NEs [303], vaccines [304], and nanoparticles [285,305].…”

Section: Mechanical Approachesmentioning

confidence: 99%

“…Microparticles and nanoparticles are being used in a new generation of MNs to help achieve long-acting benefit after delivery into the body [309]. To provide targeted and long-acting intradermal distribution of amphotericin B for the treatment of cutaneous fungal infections, dissolving MNs loaded with micronized particles of amphotericin B were developed by the Donnelly research group [301]. Amphotericin B concentrations in plasma, kidneys, liver, and spleen were significantly lower in the MN group than in the intravenous group, according to pharmacokinetic and biodistribution studies.…”

Section: Integrating Chemical and Physical Technologiesmentioning

confidence: 99%

“…Amphotericin B concentrations in plasma, kidneys, liver, and spleen were significantly lower in the MN group than in the intravenous group, according to pharmacokinetic and biodistribution studies. As a result, this approach addressed the systemic adverse effects of intravenous amphotericin B injections by localizing the drug for a week inside the skin [301].…”

Section: Integrating Chemical and Physical Technologiesmentioning

confidence: 99%

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Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

et al. 2022

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The ideal drug delivery system has a bioavailability comparable to parenteral dosage forms but is as convenient and easy to use for the patient as oral solid dosage forms. In recent years, there has been increased interest in transdermal drug delivery (TDD) as a non-invasive delivery approach that is generally regarded as being easy to administer to more vulnerable age groups, such as paediatric and geriatric patients, while avoiding certain bioavailability concerns that arise from oral drug delivery due to poor absorbability and metabolism concerns. However, despite its many merits, TDD remains restricted to a select few drugs. The physiology of the skin poses a barrier against the feasible delivery of many drugs, limiting its applicability to only those drugs that possess physicochemical properties allowing them to be successfully delivered transdermally. Several techniques have been developed to enhance the transdermal permeability of drugs. Both chemical (e.g., thermal and mechanical) and passive (vesicle, nanoparticle, nanoemulsion, solid dispersion, and nanocrystal) techniques have been investigated to enhance the permeability of drug substances across the skin. Furthermore, hybrid approaches combining chemical penetration enhancement technologies with physical technologies are being intensively researched to improve the skin permeation of drug substances. This review aims to summarize recent trends in TDD approaches and discuss the merits and drawbacks of the various chemical, physical, and hybrid approaches currently being investigated for improving drug permeability across the skin.

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Section: Mechanical Approachesmentioning

confidence: 99%

Section: Integrating Chemical and Physical Technologiesmentioning

confidence: 99%

Section: Integrating Chemical and Physical Technologiesmentioning

confidence: 99%

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Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

et al. 2022

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“…Current microneedle studies have mainly focused on the delivery of insulin [ 8 , 13 , 14 ] and vaccines [ 15 , 16 ], antibodies for cancer immunotherapy [ 17 ], and high molecular weight drugs [ 18 ]. A few microneedle studies have been published that aim to control bacterial and fungal biofilms, and have mainly focused on delivering antibiotics [ 19 ], antifungal agents [ 20 ], carvacrol [ 21 ], silver nanoparticles [ 22 ], elevating oxygenation [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Antibiofilm Efficacy of the Pseudomonas aeruginosa Pbunavirus vB_PaeM-SMS29 Loaded onto Dissolving Polyvinyl Alcohol Microneedles

Sillankorva

Pires

Pastrana

et al. 2022

Viruses

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Resistant bacteria prevail in most chronic skin wounds and other biofilm-related topical skin infections. Bacteriophages (phages) have proven their antimicrobial effectiveness for treating different antibiotic-resistant and multidrug-resistant bacterial infections, but not all phages are effective against biofilms. Phages possessing depolymerases can reach different biofilm layers; however, those that do not have depolymerase activity struggle to penetrate and navigate in the intricate 3D biofilm structure and mainly infect bacteria lodged in the outer biofilm layers. To address this, Pseudomonas aeruginosa phage vB_PaeM-SMS29, a phage with poor antibiofilm properties, was incorporated into polyvinyl alcohol (PVA, Mowiol 4:88) supplemented with 0.1% (v/v) of glycerol, and cast onto two different microneedle arrays varying in geometry. The dissolving microneedles were thoroughly characterized by microscopy, force-displacement, swelling, phage release and stability. Furthermore, 48 h-old biofilms were formed using the colony biofilm procedure (absence of broth), and the antibiofilm efficacy of the phage-loaded microneedles was evaluated by viable cell counts and microscopy and compared to free phages. The phages in microneedles were fairly stable for six months when stored at 4 °C, with minor decreases in phage titers observed. The geometry of the microneedles influenced the penetration and force-displacement characteristics but not the antimicrobial efficacy against biofilms. The two PVA microneedles loaded with phages reduced P. aeruginosa PAO1 biofilms by 2.44 to 2.76 log10 CFU·cm−2 at 24 h. These values are significantly higher than the result obtained after the treatment with the free phage (1.09 log10 CFU·cm−2). Overall, this study shows that the distribution of phages caused by the mechanical disruption of biofilms using dissolving microneedles can be an effective delivery method against topical biofilm-related skin infections.

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“…explored and demonstrated the utility of using dissolving microneedles to achieve localised and long-acting intradermal delivery of Amphotericin B, an antifungal agent, for the treatment of cutaneous fungal infections. In the work, the researchers demonstrated that the microneedles were able to be inserted into the skin to a depth of 300 µm resulting localised release of Amphotericin B into the dermis, the location where most fungal infections typically reside ( 18 ). Furthering this, Sabri et al .…”

Section: Introductionmentioning

confidence: 99%

Microneedle-Mediated Permeation Enhancement of Chlorhexidine Digluconate: Mechanistic Insights Through Imaging Mass Spectrometry

et al. 2022

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Purpose Chlorhexidine digluconate (CHG) is a first-line antiseptic agent typically applied to the skin as a topical solution prior to surgery due to its efficacy and safety profile. However, the physiochemical properties of CHG limits its cutaneous permeation, preventing it from reaching potentially pathogenic bacteria residing within deeper skin layers. Thus, the utility of a solid oscillating microneedle system, Dermapen®, and a CHG-hydroxyethylcellulose (HEC) gel were investigated to improve the intradermal delivery of CHG. Methods Permeation of CHG from the commercial product, Hibiscrub®, and HEC-CHG gels (containing 1% or 4% CHG w/w) was assessed in intact skin, or skin that had been pre-treated with microneedles of different array numbers, using an Franz diffusion cells and Time-of-Flight Secondary Ion Mass Spectrometry (ToF–SIMS). Results Gels containing 1% and 4% CHG resulted in significantly increased depth permeation of CHG compared to Hibiscrub® (4% w/v CHG) when applied to microneedle pre-treated skin, with the effect being more significant with the higher array number. ToF–SIMS analysis indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by Hibiscrub®, and showed potential lateral diffusion within the viable epidermis. Conclusions This study indicates that HEC-CHG gels applied to microneedle pre-treated skin may be a viable strategy to improve the permeation CHG into the skin. Such enhanced intradermal delivery may be of significant clinical utility for improved skin antisepsis in those at risk of a skin or soft tissue infection following surgical intervention.

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Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections

Cited by 65 publications

References 114 publications

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

Antibiofilm Efficacy of the Pseudomonas aeruginosa Pbunavirus vB_PaeM-SMS29 Loaded onto Dissolving Polyvinyl Alcohol Microneedles

Microneedle-Mediated Permeation Enhancement of Chlorhexidine Digluconate: Mechanistic Insights Through Imaging Mass Spectrometry

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