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Three-dimensional (3D) printing can be used to fabricate custom microneedle (MN) patches instead of the conventional method. In this work, 3D-printed MN patches were utilized to fabricate a MN mold, and the mold was used to prepare dissolving MNs for topical lidocaine HCl (L) delivery through the skin. Topical creams usually take 1-2 h to induce an anesthetic effect, so the delivery of lidocaine HCl from dissolving MNs can allow for a therapeutic effect to be reached faster than with a topical cream. The dissolving-MN-patch-incorporated lidocaine HCl was constructed from hydroxypropyl methylcellulose (HPMC; H) and polyvinyl pyrrolidone (PVP K90; P) using centrifugation. Additionally, the morphology, mechanical property, skin insertion, dissolving behavior, drug-loading content, drug release of MNs and the chemical interactions among the compositions were also examined. H51P2-L, H501P2-L, and H901P2-L showed an acceptable needle appearance without bent tips or a broken structure, and they had a low % height change (<10%), including a high blue-dot percentage on the skin (>80%). These three formulations exhibited a drug-loading content approaching 100%. Importantly, the composition-dependent dissolving abilities of MNs were revealed. Containing the lowest amount of HPMC in its formulation, H901P2-L showed the fastest dissolving ability, which was related to the high amount of lidocaine HCl released through the skin. Moreover, the results of an FTIR analysis showed no chemical interactions among the two polymers and lidocaine HCl. As a result, HPMC/PVP K90 dissolving microneedles can be used to deliver lidocaine HCl through the skin, resulting in a faster onset of anesthetic action.

RESUMEN

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.

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TEMPO-oxidization and mechanical disintegration were utilized to develop sacchachitin nanofibers (SCNF) with a 3D gel structure for being an ideal scaffold. Mechanically disintegrated SCNF (MDSCNF) with NanoLyzer® at 20,000 psi for 5 cycles and TEMPO-oxidized SCNF (TOSCNF) produced with 5.0 and 10.0 mmole NaClO/g SC was designated as SCN5, T050SC, and T100SC, respectively. All 2% MDSCNF suspensions were demonstrated to be in gel form, while all except T100SC of 2% TOSCNF suspensions showed to be wet fiber-like hydrogel. In diabetic wound healing study, both SCN5 and T050SC incorporated in AMPS (2-acrylamide-2-methyl-propane sulfonate)-based wound dressing were showed to accelerate diabetic wound healing forming nearly the same as normal tissues. T050SC/H further provided the healed wound with growth of sweat glands and hair follicles indicating the wound had healed as functional tissue. Conclusively, TEMPO-oxidized SCNF-based hydrogel scaffolds showed greater potentials in tissue regeneration due to its unique physical and chemical properties.

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Usnic acid (UA) is a lichenic secondary metabolite useful for the treatment of burn wounds thanks to its antimicrobial activity, particularly toward strains responsible for their infections. However, the poor solubility is the main factor limiting the activity and thus its use in health care products. Adhesive polymeric films were designed to improve UA use by enhancing its bioavailability in the wounded tissues. Three different NaCMC hydrogel films, NaCMC 2% alone (F1), mixed to PVP K90 0.1% (F2) or to Carbopol 971 P 0.1% (F3), were prepared by casting method. Ex vivo experiments performed on pig skin samples showed their suitable adhesion capacity. in vitro release test, performed using the extraction cell, showed that film F2 provides the highest UA concentrations. Differential scanning calorimetry and X-ray analyses performed on the three films highlighted that UA is present in a more soluble form in F2. The in vitro antibacterial activity studies demonstrated that F2 is the most effective film against UA sensitive bacteria S. Epidermidis, E. Faecalis, B. Cereus and S. Pyogenes. In vitro cytotoxicity assays on human keratinocytes and fibroblasts showed that cells viability is not compromised.

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