Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted microbubble destruction prevent diabetic nephropathy through inhibition of inflammation

Abstract

Basic fibroblast growth factor (bFGF) has shown great therapeutic effects for diabetic nephropathy (DN). However, its clinical applications are limited due to its short half-life, low stability and poor penetration. Herein, a bFGF-loaded liposome (bFGF-lip) was constructed and combined with ultrasound-targeted microbubble destruction (UTMD) to overcome these drawbacks. bFGF-lip exhibited spherical morphology with a diameter of 171.1 ± 14.2 nm and a negative zeta potential of -5.15 ± 2.08 mV, exhibiting a sustained-release profile of bFGF. DN rat models were successfully induced by streptozotocin. After treatment with bFGF-lip + UTMD, the concentration of bFGF in kidney of DN rats was significantly enhanced in comparison with free bFGF treatment. Additionally, the morphology and the function of the kidneys were obviously recovered after bFGF-lip + UTMD treatment as shown by ultrasonography and histological analyse. The molecular mechanism was associated with the inhibition of renal inflammation. After treatment with bFGF-lip + UTMD, the activation of NF-κB was obviously reduced in the renal tissues, and downstream inflammatory mediators including TGF-β1, MCP-1, IL-6 and IL-1β were also down regulated. In addition, inflammation-induced cellular apoptosis of renal tubular cells was also significantly inhibited by detecting Bax, caspase-3 and Bcl-2. Therefore, bFGF-lip in combination with UTMD might be a potential strategy to reverse the progression of early DN.

Combined treatment with ultrasound-targeted microbubble destruction technique and NM-aFGF-loaded PEG-nanoliposomes protects against diabetic cardiomyopathy-induced oxidative stress by activating the AKT/GSK-3β1/Nrf-2 pathway

“…Ultrasound-targeted microbubble destruction (UTMD) is a useful tool to promote the specific delivery of therapeutics to some organs. Several studies have shown that UTMD can obviously improve the organ specificity of in vivo drug release from liposomes (Sheng et al., 2018 ). After intravenous injection, microbubbles can arrive at the myocardial tissue and be destroyed by an ultrasound beam, and the resultant cavitation effect is able to enhance the release of drug from liposome in the ultrasonic sites (Miller & Dou, 2009 ; Panje et al., 2012 ; Lentacker et al., 2014 ).…”

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

“…On the other hand, treatment with bFGF alleviated oxidative stress and apoptosis in the kidney in db/db mice [58]. In a model of streptozotocin-induced diabetes in Sprague-Dawley rats, bFGF delayed the progression of diabetic nephropathy, possibly by inhibiting NF-κB and silencing of TGF-β1, MCP-1, IL-6, and IL-1β [59]. Perhaps this cytokine plays a dual role in the development of diabetic nephropathy.…”

The promising shadow of microbubble over medical sciences: from fighting wide scope of prevalence disease to cancer eradication

“…US-induced microbubble destruction is also expected to play a pivotal role in all aspects of diabetes therapy in the coming years. Several other systematic reviews shed light on the significant benefits of such an approach in patients with diabetes [ 205 – 208 ]. Two hundred thousand people are affected by diabetes, which is the sixth most commonly debilitating condition in the world.…”