Manita Dangol

A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery

Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report “Microlancer”, a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second.

A Minimally Invasive Blood-Extraction System: Elastic Self-Recovery Actuator Integrated with an Ultrahigh- Aspect-Ratio Microneedle

A minimally invasive blood-extraction system is fabricated by the integration of an elastic self-recovery actuator and an ultrahigh-aspect-ratio microneedle. The simple elastic self-recovery actuator converts finger force to elastic energy to provide power for blood extraction and transport without requiring an external source of power. This device has potential utility in the biomedical field within the framework of complete micro-electromechanical systems.

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.

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.

Development of a quantitative method for active epidermal growth factor extracted from dissolving microneedle by solid phase extraction and liquid chromatography electrospray ionization mass spectrometry

Dissolving microneedle (DMN), a transdermal drug delivery in which biological drugs are encapsulated in biodegradable and biocompatible polymers, was fabricated using epidermal growth factor (EGF) as a model drug and hyaluronic acid (HA) as a backbone polymeric matrix. After mixing calibration and DMN samples with insulin, an internal standard, solid phase extraction (SPE) was performed to separate EGF and insulin from HA, and then liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) was conducted for microgram-scale quantitation. The method showed good linearity (R2=0.997) within a specified range (1-4μg). Additionally, the decrease in EGF levels during DMN fabrication was compared using the SPE/LC-ESI-MS and enzyme-linked immunosorbent assay (ELISA), a traditional analytical method. The ELISA method detected an EGF loss of only 3.88±4.67%, whereas SPE/LC-ESI-MS detected a loss of 16.75±4.39%. Qualitative analysis by circular dichroism showed wavelength shift and splitting after DMN fabrication indicating that EGF was denatured during DMN fabrication and cell viability test showed SPE/LC-ESI-MS is more accurate and reliable for detecting the amount of active EGF loaded into the DMN than ELISA.