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WIREs Nanomed Nanobiotechnol
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Recent advances in combination of microneedles and nanomedicines for lymphatic targeted drug delivery

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Abstract Numerous diseases have been reported to affect the lymphatic system. As such, several strategies have been developed to deliver chemotherapeutics to this specific network of tissues and associated organs. Nanotechnology has been exploited as one of the main approaches to improve the lymphatic uptake of drugs. Different nanoparticle approaches utilized for both active and passive targeting of the lymphatic system are discussed here. Specifically, due to the rich abundance of lymphatic capillaries in the dermis, particular attention is given to this route of administration, as intradermal administration could potentially result in higher lymphatic uptake compared to other routes of administration. Recently, progress in microneedle research has attracted particular attention as an alternative for the use of conventional hypodermic injections. The benefits of microneedles, when compared to intradermal injection, are subsequently highlighted. Importantly, microneedles exhibit particular benefit in relation to therapeutic targeting of the lymphatic system, especially when combined with nanoparticles, which are further discussed. However, despite the apparent benefits provided by this combination approach, further comprehensive preclinical and clinical studies are now necessary to realize the potential extent of this dual‐delivery platform, further taking into consideration eventual usability and acceptability in the intended patient end‐users. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Schematic representation of; the lymphatic system throughout the human body (a), the skin structure containing dermal lymphatic network (b), and the detail of dermal lymphatic capillaries showing the vessels anchoring to surrounding collagen and elastin via the anchoring filament (c), respectively. (O'Donnell, Rasmussen, & Sevick‐Muraca, 2017; Sabri et al., 2020)). The figure is reprinted with permission of the publisher from the reference
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In vivo biodistribution (a) and the fluorescence intensity (b) of doxorubicin in lymph nodes (LN), heart (H), kidney (K), spleen (S), and liver (L) of rats following the administration of DOX‐T, DOX‐T/IV, and DOX‐T/MN (Yang et al., 2019). All figures are reprinted with permission of the publisher from the references
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In vivo imaging system images of lymph nodes, spleens, livers, and kidneys of male and female mice after 48‐hr the administration of different treatment, namely control (no MN treatment) (A), MNs laden with RhB nanoparticles (B) and MNs laden with free‐RhB (C) (a). The concentrations of photons of RhB delivered per mass of tissue in the superficial parotid lymph nodes following the administration of MNs laden with RhB nanoparticles and MNs laden with free‐RhB (b) (Kennedy et al., 2017). The amount of rilpivirine detected in excised lymph nodes in rats treated for 7, 28 or 56 days after the administration of MN containing rilpivirine nanosuspension (A) and intramuscular injection of rilpivirine (B) (c) (McCrudden et al., 2018). The concentration of DOX (A), DEC (B), ABZ‐sulfoxide (C), and ABZ‐sulfone (D) after oral treatment of drug suspensions and drug‐loaded SLNs incorporated with MNs. The lymphatic relative bioavailability of DOX, DEC and ABZ‐OX (E) after the application of drug‐loaded SLNs incorporated with MNs in comparison with the oral administration of pure drugs (d) (Permana, Tekko, et al., 2019). All figures are reprinted with permission of the publisher from the references
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Scanning electron micrograph of PLGA nanoparticles‐loaded bilayer MNs (a) and the VD3 concentration detected in different layers of excised neonatal porcine skin after the administration of PLGA nanoparticles‐loaded bilayer compared to control patch (b) (Vora et al., 2017). All figures reprinted with permission of the publisher from the reference
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Representation illustration of five type MN device. Solid MNs utilized for pre‐treatment in the skin and application of drug‐loaded reservoir (a), coated MNs for deposition of drug‐containing layer into the skin, followed by removal of the MN array (b), dissolving MNs utilized to achieve controlled or rapid delivery of drug (c), hollow MNs utilized to create holes as conduits in the skin and permit delivery of a liquid drug via the hole created (d) and hydrogel‐forming MNs utilized to deliver drugs from a drug reservoir via the hydrogel matrix (e). Taken from (M. Sharma, 2019). The figure is reprinted with permission of the publisher from the reference
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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