Yonghao Ma

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery.

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.

Physicochemical study of ascorbic acid 2-glucoside loaded hyaluronic acid dissolving microneedles irradiated by electron beam and gamma ray

A dissolving microneedle (DMN) patch encapsulated with ascorbic acid 2-glucoside (AA2G) in a needle-shaped hyaluronic acid (HA) backbone was fabricated and sterilized by electron beam (e-beam, 5-40kGy) and gamma ray (γ-ray, 5-30kGy). DMN structures maintained their morphologies and fracture force regardless of e-beam and γ-ray irradiation doses. Both e-beam (40kGy) and γ-ray (20 and 30kGy) met the product sterility requirements for cosmetics and vaccines; however, γ-ray irradiation significantly degraded the encapsulated AA2G, while e-beam maintained AA2G activity. Thus, an e-beam dose of 40kGy, which satisfied the sterility requirements without loss of AA2G, is suitable for terminal sterilization of DMNs. Moreover, we confirmed that the optimized irradiation (e-beam, 40kGy) did not affect dissolution rate and drug release profile of DMNs. Further, we confirmed that HA, the backbone polymer of DMNs, could be utilized as a stabilizer that inhibits degradation of encapsulated AA2G by irradiation. This detailed analysis can be developed further to optimize various biological drugs in transdermal drug delivery systems.

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.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) antibody via Tower Microneedle

Tower Microneedle was developed with minimal ocular tissue damages even reflux, while no study was reported with intravitreal injection of ophthalmic drug via Tower Microneedle into the eye. Intravitreal injection of anti-vascular endothelial growth factor antibodies via the Tower Microneedle or a 30-G hypodermic needle was performed 1 week after argon laser irradiation into the retina of the mouse models. Less bleb formation was occurred with Tower Microneedle than 30-G hypodermic needle, while both needles led to comparable degrees of anti-angiogenesis in the retina after intravitreal injection of anti-vascular endothelial growth factor antibodies over 100 ng/μL concentration. Conclusively, the Tower Microneedle can deliver anti-vascular endothelial growth factor antibody into the posterior segment of the eye with minimal bleb formation after intravitreal injection.