Hyaluronidase-powered microneedles for significantly enhanced transdermal delivery efficiency

Hu, Wanshan; Peng, Tingting; Huang, Yao; Ren, Tao; Chen, Hongyu; Chen, Yangyan; Feng, Disang; Wu, Chuanbin; Pan, Xin

doi:10.1016/j.jconrel.2022.11.046

Cited by 13 publications

(5 citation statements)

References 46 publications

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“…The authors developed mechanically robust hyaluronidase-powered microneedles, which provided efficient skin poration and enhanced transdermal delivery of macromolecules. Hyaluronidase depolymerizes hyaluronic acid in the skin tissue to expand the subcutaneous space and disrupt the extracellular matrix barrier, thus improving drug permeation [ 215 ]. Panda et al fabricated biodegradable and biocompatible microneedles from poly (D, L-lactic co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) using a mold-casting method.…”

Section: Microneedle Types For Biopharmaceutical Deliverymentioning

confidence: 99%

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

Nguyen

2023

Pharmaceutics

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Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

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Section: Microneedle Types For Biopharmaceutical Deliverymentioning

confidence: 99%

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

Nguyen

2023

Pharmaceutics

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“…Based on the fact that the TPC@HAT nanosystem can effectively target and accumulate at the RA joint site and subsequently respond to the biomarkers (HAase and H 2 O 2 ) at the RA joint site, we utilized the nanosystem TPC@HAT to image the RA site in the ZIA mouse model. It is well known that ROS (such as H 2 O 2 ) and hyaluronidase are overexpressed in joint region of RA, and thus the H 2 O 2 or hyaluronidase can act as endogenous biomarkers for RA [46][47][48][49][50][51] The experimental protocol is illustrated in Figure 5A. To induce rheumatoid arthritis in mice, we administered zymosan intraarticularly at varying doses for 24 hours.…”

Section: Tpc@hat's In Vivo Targeting Capability and Imaging In Zymosa...mentioning

confidence: 99%

“…The RA microenvironment has high levels of reactive oxygen species (referred to as ROS, with H 2 O 2 being the most abundant and stable ROS member) [46][47][48] and overexpressed enzymes (e.g., hyaluronidase). [49][50][51] Hence, using in-situ H 2 O 2 and HAase as dual pathological stimuli is an ideal approach to precisely trigger on-demand drug release at the site of RA lesions.…”

Section: Introductionmentioning

confidence: 99%

A multifunctional nanoaggregate‐based system for detection of rheumatoid arthritis via Optoacoustic/NIR‐II fluorescent imaging and therapy via inhibiting JAK‐STAT/NF‐κB/NLRP3 pathways

Chen,

She

et al. 2023

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Rheumatoid arthritis (RA) is a debilitating autoimmune disease that causes chronic pain and serious complications, presenting a significant challenge to treat. Promising approaches for treating RA involve signaling pathways modulation and targeted therapy. To this end, a multifunctional nanosystem, TPC‐U@HAT, has been designed for RA therapy, featuring multitargeting, dual‐stimuli response, and on‐demand drug release capabilities. TPC‐U@HAT is composed of a probe/prodrug TPC, a JAK1 kinase inhibitor upadacitinib, and the drug carrier HAT. TPC is composed of an aggregation‐induced emission (AIE)‐active NIR‐II chromophore TPY and an NF‐κB/NLRP3 inhibitor caffeic acid phenethyl ester (CAPE), connected via boronic ester bond which serves as the reactive‐oxygen‐species‐responsive linker. The carrier, HAT, is created by grafting bone‐targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains, which can encapsulate TPC and upadacitinib to form TPC‐U@HAT. Upon intravenous injection into mice, TPC‐U@HAT accumulates at inflamed lesions of RA through both active and passive targeting, and the overexpressed hyaluronidase and H2O2 therein cleave the hyaluronic acid polymer chains and boronate bonds, respectively. This generates an AIE‐active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR‐II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF‐κB/NLRP3 and JAK‐STAT pathways.

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“…When HAase meets HA in the dermis, HA is depolymerized under the depolymerization action of HAase. Then the dermis tissue is loosened, and the ECM barrier is destroyed, resulting in enhancing a larger area of drug diffusion and deeper penetration distance [ 28 ]. Since the discovery of the biological activity of HAase, it was also clinically used in the treatment of chemotherapy extravasation [ 29 ], hypertrophic scar [ 30 ], local scleroderma, melanoma [ 31 ], and other diseases due to its optimistic effect on enhancing diffusion kinetics.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, combination therapy is also an important means of HAase application as well [ 32 , 33 ]. Co-loading HAase and hydrophilic metformin hydrochloride into MNs could significantly improve the efficiency of transcutaneous penetration [ 28 ]. However, as we know, most active pharmaceutical ingredients are poorly water soluble, and HAase loaded in MNs may increase the penetration of this kind of drug.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronidase Promote Transdermal Diffusion of Small Sized Curcumin Nanocrystal by Dissolving Microneedles Delivery

et al. 2023

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Hyaluronidase is clinically used in treating many skin diseases due to its good permeability-promoting effect, which may motivate the diffusion and absorption of drugs. To verify the penetration osmotic effect of hyaluronidase in microneedles, 55 nm-size curcumin nanocrystals were fabricated and loaded into microneedles containing hyaluronidase in the tip. Microneedles with bullet shape and backing layer of 20% PVA + 20% PVP K30 (w/v) showed excellent performance. The microneedles were able to pierce the skin effectively with a skin insert rate of 90% and demonstrated good mechanical strength. In the in vitro permeation assay, with the increase of hyaluronidase concentration at the tip of the needle, the cumulative release of curcumin increased, as well as the skin retention decreased. In addition, compared with the microneedles without hyaluronidase, the microneedles containing hyaluronidase in the tip exhibited a larger drug diffusion area and deeper diffusion depth. In conclusion, hyaluronidase could effectively promote the transdermal diffusion and absorption of the drug.

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Hyaluronidase-powered microneedles for significantly enhanced transdermal delivery efficiency

Cited by 13 publications

References 46 publications

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

A multifunctional nanoaggregate‐based system for detection of rheumatoid arthritis via Optoacoustic/NIR‐II fluorescent imaging and therapy via inhibiting JAK‐STAT/NF‐κB/NLRP3 pathways

Hyaluronidase Promote Transdermal Diffusion of Small Sized Curcumin Nanocrystal by Dissolving Microneedles Delivery

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