Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats

Abstract

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.

Rational Design of Rapidly Separating Dissolving Microneedles for Precise Drug Delivery by Balancing the Mechanical Performance and Disintegration Rate

“…Physical Morphology of the Prepared DMNs : The physical morphology of the prepared DMNs were observed by SEM (JSM‐6330F, Jeol, Tokyo, Japan) and Stereo Fluorescence microscope (SteREO Lumar V12, Zeiss, Germany) . The heights of the individual parts were measured by the laser scanning confocal microscope (LSM710, Zeiss, Germany) and calculated using Image J.…”

“…Recently, the dissolving microneedles (DMNs) have been proved to remarkably enhance the transdermal drug penetration due to their ability to break the skin's stratum corneum barrier by generating mechanical micropores . Moreover, DMNs offer several advantages superior to hypodermic injection and oral administration, including ease of administration, minimal pain, and avoidance of first pass effect .…”

Recent advances of microneedles for biomedical applications: drug delivery and beyond

“…The shape and tips of microneedles are largely determined by the needle geometry devised upon the basis of simulation software. Silicon microneedles were fabricated in 1998 using ion etching method employing a conventional dry-etching process, which was a costly fabrication progress 14 . To get rid of this limit, the super-short microneedles were successfully manufactured using wet etching of silicon in 30% KOH at 80 °C 39 .…”

“…This new POC device by integrating hollow microneedle with a microfluidic chip has a potential for disease diagnostic. Together, the diversity of microneedle manufaction and the performance of different microneedle were shown in Table 2 14 , 39 , 42 , 49 , 51 , 54 , 55 , 58 , 59 , 60 , 61 , 62 , 63 , 64 .…”

“…Other penetration-enhancing methods, such as iontophoresis, sonophoresis, and electrophoresis mainly caused a severe damage to stratum corneum structure 13 . As one of the robust routes for drug delivery, transdermal drug delivery systems (TDDS) have been extraordinarily studied over the past 50 years 14 , 15 . In comparison to conventional delivery methods, the advent of microneedle-based transdermal delivery overcomes the obstacles like patient compliance, pain, the risk of infection and long-term treatment, etc 16 .…”