Enhanced therapeutic efficacy of cationic liposome-delivered nerve growth factor antisense oligonucleotide for interstitial cystitis/bladder pain syndrome

Abstract

The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, and there is no definitive treatment for this condition. Studies have shown that antisense oligonucleotide (asODN) targeting nerve growth factor (NGF) can downregulate the level of NGF in the bladder, however, the uptake of NGF asODN by the body is limited. Therefore, this study constructed cationic liposomes (CLs) as a delivery system to carry NGF asODN and evaluated its functional efficacy on the bladder. The results indicated that the optimized CLs/asODN delivery system had an average particle size of approximately 200 nm, an average zeta potential of around +53 mV, and an encapsulation efficiency of over 90% with good stability. Additionally, CLs/asODN significantly facilitated the uptake of asODN fluorescence by the urothelium, with an uptake rate of 14.6%, which was 40.2 times free asODN. In a rat model of IC/BPS, treatment with CLs/asODN reduced voiding frequency, significantly increased maximum cystometric capacity, prolonged inter-contraction interval of the bladder, and improved bladder compliance. Furthermore, hematoxylin-eosin staining and immunohistochemical analysis revealed significantly reduced expression levels of NGF, PACAP, Piezo2, CCL2, IL-6, and TGF-β factors after treatment, indicating that the overexpression of NGF in the bladder could be indirectly blocked by complexing NGF asODN with cationic liposomes. The CLs/asODN prepared in this study improved the adhesion and penetration of the drug at the bladder mucosa site, effectively alleviated bladder dysfunction in rats, and further enhanced the inhibitory effect of asODN on NGF, which may provide a new strategy for the treatment of IC/BPS.