Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release

Kim, Dae-Sung; Choi, Jun-Tae; Kim, Cheong Bi; Shin, Yura; Park, Pil-Gu; Kim, Hyemi; Lee, Jae Myun; Park, Jung Hwan

doi:10.1007/s11095-020-2768-3

Cited by 20 publications

(8 citation statements)

References 27 publications

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“…HA was utilized as the dissolvable polymer that comprises the body of the CEDMN, which was confirmed by 1 H-NMR spectroscopy. Since HA is non-immunogenic, reactions are therefore quite improbable and the product is deemed safe [12,15].…”

Section: Discussionmentioning

confidence: 99%

“…The dissolution rate of the microneedles and therefore, the drug release rate depends on the physico-chemical properties of the polymer substrate, namely on the hydrophilicity and molar mass [14]. The most frequently used material in this regard is hyaluronic acid (HA) [12], which is an endogenous linear non-sulphated glycosaminoglycan that is present ubiquitously in the body including the skin, synovial fluid, vitreous humor and even dental pulp [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles

Decker

Szabó

Hoeksema

et al. 2022

Journal of Burn Care &Amp; Research

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Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles

Decker

Szabó

Hoeksema

et al. 2022

Journal of Burn Care &Amp; Research

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“…The fluorescence quantum yield of xanthene dyes, especially rhodamines, and its derivatives is from 0.36 to 0.98 depending on the exact structure and solvent [42]. The modification of Rhodamine B by an isothiocyanate group brings opportunities to easily label various types of proteins [43], polysaccharides [44], and nanoparticles [45,46].…”

Section: Fluorescent Behavior Investigationsmentioning

confidence: 99%

Fluorescent Submicron-Sized Poly(heptafluoro-n-butyl methacrylate) Particles with Long-Term Stability

et al. 2020

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Fluorescent submicron particles of fluorinated methacrylate (HFMBA) with long-term stability have been synthesized and characterized with regard to their potential applications. Rhodamine B (RBITC) isothiocyanate was used as the fluorescent component. The core–shell structure of the particles effectively protected the dye against bleaching. HFBMA nanoparticle (NP) stability was confirmed after seven years of storage. Only slight differences were found in the polydispersity index (pdi) from 0.002 to 0.010. Particle size measurements were carried out using dynamic light scattering (DLS), nanoparticle tracking (NTA), and fluorescence correlation spectroscopy (FCS). The hydrodynamic diameter evaluated by different methods were in good agreement, respectively: 184–550 nm, 218–579 nm, and 236–508 nm. Particle and core morphology was estimated by using scanning and transmission electron microscopy (SEM and TEM). The ability to recognize particles in 3D as a reference sample in biological media has been confirmed by epifluorescence optical microscopy, confocal laser scanning microscopy, and super-resolution confocal microscopy (STED).

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“…However, user risk is the major issue with microneedles if used by the untrained, which is a major limitation [4]. Another limitation of microneedles is that they do not have a uniform penetration profile [5,6], thus it is difficult to assess the risk of systemic delivery via blood vessel penetration. Both ablative fractional laser and microneedles claim to penetrate to a maximum depth in the skin, but both are limited by not having the capacity for skin strata specific delivery of drugs due to mechanical variability of the skin, strata thickness and variations in application.…”

Section: Introductionmentioning

confidence: 99%

Elongated microparticles tuned for targeting hyaluronic acid delivery to specific skin strata

Yamada

Dang

Lin

et al. 2021

Intern J of Cosmetic Sci

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Objective: Microneedle or fractional laser applications are the most common topical delivery enhancement platforms. However, these methods of drug delivery are not skin strata specific. Drug delivery approaches which could target specific stratum of the skin remains a challenge. Elongated microparticles (EMPs) have been used in enhancing drug delivery into the skin. The aim of this study was to evaluate, for the first time, elongated silica microparticles with two different length profiles to enhance delivery of hyaluronic acid into different strata of human skin.Methods: Two types of EMPs-long (milled EMPs) or short (etched EMPs) length ranges were characterized. A prototypical liquid formulation (Fluorescent hyaluronic acid) with and without EMP enhancement were evaluated for hyaluronic acid delivery in ex-vivo human skin. High performance liquid chromatography, Typhoon fluorescence scanning system, laser scanning confocal microscopy and reflectance confocal microscopy (RCM) were used to validate F-HA stability, visualize fluorescein in the skin, image the depth of F-HA delivery in the skin and define EMP penetration in skin strata, respectively. Statistical analysis was conducted using GraphPad Prism 6 software (GraphPad Software Inc, USA). Results: Fluorescein-hyaluronic acid was stable and EMP enhanced skin penetration. RCM revealed that 'etched EMP' penetrated the skin to the stratum spinosum level. The vast majority (97.8%; p < 0.001) of the etched EMP did not penetrate completely through the viable epidermis and no obvious penetration into the dermis. In contrast, milled EMP showed 41-fold increase in penetration compared to the etched EMP but penetrated beyond the dermoepidermal junction. Conclusion:EMPs can enhance delivery of hyaluronic acid. Using EMPs with defined length distributions, which can be tuned for a specific stratum of the skin, can achieve targeted hyaluronic acid delivery.

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Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release

Cited by 20 publications

References 27 publications

Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles

Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles

Fluorescent Submicron-Sized Poly(heptafluoro-n-butyl methacrylate) Particles with Long-Term Stability

Elongated microparticles tuned for targeting hyaluronic acid delivery to specific skin strata

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