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International Journal of Bioprinting                                Transdermal vitamin C delivery by MNPs




            as skin erythema, dryness, epidermal breakage, wrinkled   skin puncture by pressing and somewhat limits the
            roughness, and pigmentation. Prolonged exposure to UV   application to large areas of curved skin. 17,18  Therefore,
            radiation can potentially lead to  skin cancer.  The UV   the development of novel transdermal delivery strategies
                                                 1,2
            spectrum comprises three different types of UV categorized   based on the structural characteristics of microneedles
            by ranges of wavelength: UVA (320–400 nm), UVB (280–  maintains considerable importance.
            320 nm), and UVC (100–280 nm).  The ozone layer acts   The recent progress in the research of transdermal
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            as a barrier that prevents the penetration of UVC, which   microneedle particles (MNPs) merits significant attention.
            has a shorter wavelength, into the skin’s epidermis. On the   These MNPs are typically used in conjunction with
            other hand, UVA with a longer wavelength can reach the   ointment applied through smearing. In addition to the
            dermis, but its biological activity is significantly lower than   advantages of conventional microneedles, MNPs are also
            UVB. Consequently, UVB is the primary culprit behind
            skin photodamage. 4,5                              suitable for large and curved skin, requiring only hand
                                                               application without auxiliary devices. The MNPs used to
               When the skin is exposed to excessive UVB radiation,   enhance  the  skin  permeability  include  sponge  Haliclona
            the accumulation of reactive oxygen species (ROS) leads to   sp. spicules (SHS),  elongated microparticles (EMPs),
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            oxidative stress. Moreover, ROS-mediated oxidative stress   microneedle-like particles (MLP),  and star-shaped
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            can cause lipid peroxidation and DNA damage. Once DNA   particles (STAR particles).  Nevertheless, it is challenging
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            damage is irreparable, cells will undergo necrosis or genetic   to rapidly and cost-effectively fabricate customized MNPs,
            mutations. Therefore, the development of pharmaceutical   and the processes are cumbersome and costly, in addition
            agents aimed at preventing and treating photodamage holds   to the difficulties they are facing in large-scale preparations,
            significant clinical value. The incorporation of antioxidants   materials, and morphological structures.
            into cosmetic products and their topical application to the
            skin after sunburn have attracted substantial attention   In view of the above, we decided to fabricate MNPs
            and spawned a series of research on skin photodamage   using polymer materials due to their  wide applications
            management.  Currently, low-molecular-weight antioxidants,   in biomedical fields. Additionally, the development of
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            like vitamin C, are the most widely used antioxidant-based   polymeric MNPs has a promising prospect of applications.
            skin damage drugs. They have been proven to effectively   At the same time, additive manufacturing is an emerging
            reduce DNA damage, promote DNA excision repair, and   technology capable  of better control of  the  shape,  size,
            inhibit inflammation and cell proliferation. Topical vitamin   projection length, and other parameters of MNPs. It can
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            C has been used to prevent the formation of erythema   simplify the production process as well as reduce the cost.
            as well as sun-damaged cells and to upregulate collagen   Our group has developed a novel digital light processing
            production.  However, vitamin C is a water-soluble charged   (DLP)-based  3D  printing  technique 25,26   that  avoids  the
                     7
            molecule repelled by the stratum corneum barrier. Therefore,   generation of stepped layered structure, a common
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            the  development  of  a  novel  transdermal  antioxidant  drug   occurrence with traditional 3D printing technology.  The
            delivery strategy is of utmost significance.       latter can affect the mechanical properties of microneedles
                                                               and lead to fracture if a high printing speed is applied.
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               Transdermal drug delivery (TDD) is a drug delivery
            method that involves administering drugs through the   In this study, we utilized a DLP-based micro-printing
            skin. It avoids the first-pass effect of the intestines and   process to precisely customize MNPs with needle-like
            liver, reduces adverse reactions, and improves patient   structures. The MNPs are typically less than 1 mm in
            compliance.  Nevertheless, TDD faces specific challenges,   diameter, and their projection lengths vary from 100 to
                      8
            since the skin barrier function limits the transdermal   600 μm. They can be fabricated by using photosensitive
            absorption of most drugs.  Only small-molecule,    materials in less than 5 s, then formulated in a medicated
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            lipophilic, and low-dose drugs can effectively penetrate   ointment, and smeared painlessly to break through
            the stratum corneum and enter the blood circulation.   the stratum corneum barrier efficiently, significantly
            Numerous  emerging  TDD  techniques  have  developed   increasing skin permeability. In addition, the skin can also
            rapidly in recent years, such as chemical penetration   be pre-treated with MNPs to facilitate drug penetration.
            enhancers,  laser-assisted delivery,  iontophoresis,    This process allows the customized preparation of
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            sonophoresis,  microneedle, 14,15  and electroporation.    large batches of MNPs within seconds. It provides a solid
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               Currently, microneedle technology has attracted wide   basis  for their  large-scale  production while  ensuring
            attention in direct physical enhancement to promote   the  high  precision  indispensable  for  the  manufacturing
            drug absorption and plays an important role in the field   of  high-quality MNPs. More  importantly,  MNPs  with
            of medicine. However, using as a microneedle array often   needle-like  structures  may improve the  penetration into
            requires a specific auxiliary device to achieve effective   the stratum corneum, thereby effectively delivering more
            Volume 10 Issue 1 (2024)                       358                          https://doi.org/10.36922/ijb.1285
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