Mingyu Jang

Centrifugal Lithography: Self-Shaping of Polymer Microstructures Encapsulating Biopharmaceutics by Centrifuging Polymer Drops

Polymeric microstructures encapsulating biopharmaceutics must be fabricated in a controlled environment to preserve the biological activity. There is increasing demand for simple methods designed to preserve the biological activity by utilizing the natural properties of polymers. Here, the paper shows that centrifugal lithography (CL) can be used for the fabrication of such microstructures in a single centrifugation, by engineering the self-shaping properties of hyaluronic acid (HA). In this method, HA drops are self-shaped into hourglass-microstructures to produce two dissolving microneedles (DMN), which facilitate transdermal delivery via implantation on the skin. In addition, tuberculin purified protein derivatives are encapsulated into HA DMNs under refrigerated conditions (4 °C) during CL. Therefore, the tuberculin skin test (TST) with the DMNs indicates minimal damage, as opposed to the case of TST with traditional hypodermic needles. These findings on the fabrication of polymeric microstructures with biopharmaceutics may trigger the development of various biomedical devices and therapies.

Anti-obesity effect of a novel caffeine-loaded dissolving microneedle patch in high-fat diet-induced obese C57BL/6J mice

Abstract Natural products such as caffeine have been found to be effective in reducing body weight through lipolysis. Here, we report the successful loading of caffeine onto dissolving microneedle following inhibition of its crystal growth by hyaluronic acid (HA), the matrix material of the dissolving microneedle (DMN). Further, the anti‐obesity activity of caffeine was evaluated in high‐fat diet‐induced obese C57BL/6J mice. After 6 weeks of caffeine loaded dissolving microneedle patch (CMP) administration, lipolysis improved significantly as shown by leptin and adiponectin activity, which resulted in considerable weight loss of about 12.8 ± 0.75% in high‐fat diet‐induced obese mice. Comparison of the levels of triglyceride, total cholesterol, high‐density lipoprotein (HDL)‐cholesterol, and low‐density lipoprotein (LDL)‐cholesterol after CMP administration with the initial levels in obese mice indicated significant anti‐obesity activity of CMP. These findings suggested that a novel CMP with an increased amount of caffeine loaded onto DMN has therapeutic activity against obesity. Graphical abstract Figure. No Caption available.

Effects of two droplet-based dissolving microneedle manufacturing methods on the activity of encapsulated epidermal growth factor and ascorbic acid

Abstract Dissolving microneedle (DMN) is an attractive, minimally invasive transdermal drug delivery technology. The drugs encapsulated in the DMNs are exposed to a series of thermal, chemical, and physical stresses during the fabrication process, decreasing their therapeutic activity. Current DMN fabrication methods, such as micro‐molding, drawing lithography, droplet‐born air blowing, and centrifugal lithography, undergo different manufacturing processes involving differing stress conditions. Among the methods, we compared the effects of two droplet‐based methods, droplet‐born air blowing and centrifugal lithography, on the activity of encapsulated drugs using epidermal growth factor and ascorbic acid as model drugs. Although the appearance and physical properties of DMNs fabricated by the two methods were similar, the immunoreactivity of encapsulated epidermal growth factor in centrifugal lithography and droplet‐born air blowing was 92.08 ± 2.86% and 80.67 ± 8.00%, respectively, at baseline, and decreased to 75.32 ± 19.40% and 41.75 ± 16.17%, respectively, 24 h after drug‐loading. The free‐radical scavenging activity of ascorbic acid was maintained at 88.24 ± 0.78% in DMNs fabricated by centrifugal lithography, but decreased over time to 67.02 ± 1.11% in DMNs fabricated by droplet‐born air blowing. These findings indicate that the manufacturing conditions of centrifugal lithography exert less stress on the drug‐loaded DMNs, minimizing activity loss over time, and therefore that centrifugal lithography is suitable for fabricating DMNs loaded with fragile biological drugs. Graphical abstract Figure. No caption available.

Exendin-4-encapsulated dissolving microneedle arrays for efficient treatment of type 2 diabetes

Dissolving microneedles (DMNs) are microscopic needles capable of delivering encapsulated compounds and releasing them into the skin in a minimally invasive manner. Most studies indicate that encapsulating therapeutics in DMNs is an efficacious approach; however, the importance of evaluating the activity of encapsulated compounds, during the fabrication process, has not been examined in detail. Conducting an analysis of thermal, chemical, and physical stress factors, including temperature, pH, and the interaction of the polymer and therapeutics mixture during preparation, is essential for retaining the activity of encapsulated therapeutics during and after fabrication. Here, we optimised the thermal, chemical, and physical parameters for the fabrication of exendin-4 (Ex-4)–encapsulated DMNs (Ex-4 DMNs). Ex-4, a peptide agonist of glucagon-like peptide (GLP) receptor, is used for glycaemic control in patients with type 2 diabetes. Our findings indicate that optimising the parameters involved in DMN fabrication retained the activity of Ex-4 by up to 98.3 ± 1.5%. Ex-4 DMNs reduced the blood-glucose level in diabetic mice with efficiency similar to that of a subcutaneous injection. We believe that this study paves way for the commercialisation of an efficient and minimally invasive treatment for patients with type 2 diabetes.

Effects of dissolving microneedle fabrication parameters on the activity of encapsulated lysozyme

&NA; Dissolving microneedle (DMN) is referred to a microscale needle that encapsulates drug(s) within a biodegradable polymer matrix and delivers it into the skin in a minimally invasive manner. Although vast majority of studies have emphasized DMN as an efficient drug delivery system, the activity of DMN‐encapsulated proteins or antigens can be significantly affected due to a series of thermal, physical and chemical stress factors during DMN fabrication process and storage period. The objective of this study is to evaluate the effects of DMN fabrication parameters including polymer type, polymer concentration, fabrication and storage temperature, and drying conditions on the activity of the encapsulated therapeutic proteins by employing lysozyme (LYS) as a model protein. Our results indicate that a combination of low temperature fabrication, mild drying condition, specific polymer concentration, and addition of protein stabilizer can maintain the activity of encapsulated LYS up to 99.8 ± 3.8%. Overall, findings of this study highlight the importance of optimizing DMN fabrication parameters and paves way for the commercialization of an efficient delivery system for therapeutics. Graphical abstract Figure. No caption available.

Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches

Background: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. Methods: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Results: Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. Conclusion: The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization.

Adenosine-loaded dissolving microneedle patches to improve skin wrinkles, dermal density, elasticity and hydration

Although dissolving microneedle patches have been widely studied in the cosmetics field, no comparisons have been drawn with the topical applications available for routine use. In this study, two wrinkle‐improving products, adenosine‐loaded dissolving microneedle patches and an adenosine cream, were evaluated for efficacy, with respect to skin wrinkling, dermal density, elasticity, and hydration, and safety in a clinical test on the crows feet area.

Two-phase delivery using a horse oil and adenosine-loaded dissolving microneedle patch for skin barrier restoration, moisturization, and wrinkle improvement

Dissolving microneedles (DMNs) have been used for skin restoration and wrinkle improvement. Although lipophilic compounds, for example, natural oils or ceramides, enrich the skin barrier, their delivery via DMNs is challenging because of DMN fabrication difficulties.