Pharmacokinetic improvement provided by microneedle patch in delivering bee venom, a case study in combating scopolamine-induced neurodegeneration in mouse model

Drug Deliv. 2022 Dec;29(1):2855-2867. doi: 10.1080/10717544.2022.2116129.

Abstract

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.

Keywords: Neurodegeneration; bee venom; melittin; microneedle patch; pharmacokinetic.

MeSH terms

  • Animals
  • Bee Venoms* / analysis
  • Bee Venoms* / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems
  • Melitten / pharmacology
  • Mice
  • Neuroprotective Agents*
  • Scopolamine

Substances

  • Bee Venoms
  • Neuroprotective Agents
  • Melitten
  • Scopolamine

Grants and funding

This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (Grant No.: HI19C0553) and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)—Nos. NRF 2022R1I1A3068255 and NRF 2021R1A2C2007041.