Much research has shown Bee venom to be an effective neuroprotective agent. However, the usual transdermal injection of bee venom poses many pharmacokinetic disadvantages. Here, we compared the administration of bee venom via subcutaneous injection (SC) and via Microneedle patch (MN). Both administrated routes produce significant recovery effects, however: the MN significantly prolongs the bio-significant-and-yet-lower concentration of bee venom in mice bodies. In contrast, SC could produce only a short period of much higher bee venom levels in the blood and brain. We also see that due to the concentration-response-curve of bee venom (represented by melittin): mice bodies do not require much higher bee venom concentration (seen in the SC group) to produce a much more significant neuroprotective effect (than seen in those treated with the MN method). Therefore, a MN could maintain bee venom levels in mice bodies at lower-yet-more-efficient concentrations. This is important, as bee venom can cause more adverse effects and pain sensations, at higher concentrations. For the first time, we confirmed that the pharmacokinetic advantages of MN delivered bee venom also guarantee a holistic neuroprotection effect (which was shown by SC delivered bee venom in previous research). This was proven via the results of the water maze experiments for long-term learning memory assessment and protein analysis of key neuronal regulatory proteins: BDNF, p-CREB, iNOS, and mArhR 1. In conclusion, for situations where we ought to administrate drugs at a more downward amount, such as bee venom, MN can keep the therapeutic concentrations at a lower, yet interestingly, more-efficient level.

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Background: Jawoongo (JW) is a topical herbal ointment that has been used as an alternative treatment option for atopic dermatitis (AD). Topical ointments are known to have less bioavailability because the stratum corneum allows only lipophilic and low molecular weight drugs to pass across it. This study aimed to investigate whether applying microneedle patches (MNPs) increases the therapeutic effect of JW for AD by enhancing transdermal delivery. Methods: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. The combination treatment of JW and MNPs was estimated to study the effect of MNPs in improving transdermal delivery. Histological analysis, real-time polymerase chain reaction (RT-PCR), and immunofluorescence were performed to verify the effect of MNPs in enhancing the therapeutic effects of JW on AD in mice. Results: Both combination treatment and JW treatment ameliorated histological alterations and reduced skin thickness and infiltration of CD4+ T cells in AD-like skin lesions in DNCB-exposed BALB/c mice. However, the improvement of histological alterations was better in the combination treatment, which was almost normal. Furthermore, the combination treatment exhibited a larger decrease in mRNA levels of IL-4, IL-6, IL-13, iNOS, and TNF-α, compared to JW only. In addition, skin thickness and infiltration of CD4+ T cells in the sensitized skin were significantly lower using the combination treatment than using JW only. Conclusion: Combination treatment with JW and MNP further decreased skin thickness and several inflammatory cytokines in AD-like skin lesions compared to that using JW alone. These findings suggest that applying a dissolvable MNP after the JW application could be useful for treating AD. Keywords: Atopic dermatitis, dissolvable microneedle patch, Jawoongo, DNCB