Research Article: Experimental verification and PK/PD modeling of selective drug absorption via acupoint administration in rabbit model of rheumatoid arthritis
Abstract:
The administration of drugs at specific acupoints is a traditional practice in Chinese medicine, yet scientific evidence supporting its pharmacokinetic and pharmacodynamic (PK/PD) advantages remains limited. This study aimed to evaluate the transdermal absorption and therapeutic effects of miRNA55 when delivered via microneedles at different acupoints in a rabbit model of rheumatoid arthritis (RA).
An RA model was established in New Zealand rabbits using ovalbumin-Freund’s complete adjuvant emulsion. miRNA55 was encapsulated in cationic liposomes and combined with hyaluronic acid for microneedle preparation. Microneedles were applied at classical acupoint (ST36), atypical acupoints (GB34), and non-acupoint areas above the knee joint of the rabbits (avoiding ST35). Drug concentrations in the joint cavity fluid were assessed by microdialysis and enzyme-linked immunosorbent assay (ELISA). The encapsulation rate and in vitro release of miRNA55 were analyzed by UV spectrophotometry. PK/PD modeling was conducted using WinNonlin 8.1, with IL-1?, TNF- ? , and IL-6 as pharmacodynamic markers. The protein expression of TNF-?, MMP-1, and MMP-3 was assessed using western blotting (WB), and histopathological changes in the synovial tissue were observed by hematoxylin–eosin (H&E) staining.
miRNA55 concentrations in the joint cavity were the highest in the ST36 group, followed by the GB34 and non-acupoint groups. This observation indicated that the degree of drug absorption. PK/PD modeling showed higher efficacy value for ST36 across all three cytokines. For IL-1?, Emax model for ST36 was E = 81.09 C e 169.56 + C e ; for TNF- ? , E = 70.35 C e 136.15 + C e ; and for IL-6, E = 69.93 C e 167.88 + C e , all higher than those observed in the GB34 and non-acupoint groups. WB analysis confirmed lower expression level of inflammatory proteins in the ST36 group. H&E staining showed reduced synovial erosion and lymphokine infiltration in the ST36 group compared to those in the other two groups.
This study demonstrates that transdermal administration of miRNA55 via microneedle at specific acupoints enhances drug absorption and improves therapeutic outcomes in a rabbit model of RA. These findings support the traditional concept of acupoint specificity and offer a scientific basis for integrating acupoint-based drug delivery in modern RA treatment strategies.
Introduction:
The administration of drugs at specific acupoints is a traditional practice in Chinese medicine, yet scientific evidence supporting its pharmacokinetic and pharmacodynamic (PK/PD) advantages remains limited. This study aimed to evaluate the transdermal absorption and therapeutic effects of miRNA55 when delivered via microneedles at different acupoints in a rabbit model of rheumatoid arthritis (RA).
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