Experimental verification and PK/PD modeling of selective drug absorption via acupoint administration in rabbit model of rheumatoid arthritis.

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).

METHODS

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-1β, TNF-α, and IL-6 as pharmacodynamic markers. The protein expression of TNF-α, 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.

RESULTS

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-1β, Emax model for ST36 was E = 81.09 C e 169.56 + C e ; for TNF-α, 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.

DISCUSSION: 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.