| Nanomaterials drug delivery systems,such as liposomes,micelles and solid lipid nanoparticles,have good biocompatibility and biodegradability.When they are used as carriers to encapsulate drugs,they can control drug release and improve drug bioavailability.Dexamethasone(Dex)is an anti-inflammatory glucocorticoid,which is often used to treat rheumatoid arthritis.Dex can reduce the vascular permeability of inflammatory tissue and inhibit the proliferation of fibroblasts,but the treatment efficiency is reduced because of the nonspecific distribution of Dex after entering the human body.Using nanomaterials to deliver dexamethasone can effectively improve the therapeutic effect,but the lack of ligand modification makes nanomaterials have no active targeting ability.The content of albumin in blood is extremely high,and it can accumulate significantly in inflammatory sites.Modification of nanomaterials with albumin can enhance its active targeting ability.Therefore,we designed albumin binding domain(ABD)modified dexamethasone liposome(ABD-LIP/Dex).The liposome can specifically combine with endogenous albumin in blood and target to the inflammatory joint to improve the concentration of the drug in the inflammatory joint so as to enhance the therapeutic effect of the drug.In this paper,ABD-Lip/Dex was first prepared by thin film dispersion method and characterized by a series of measurements,such as particle size,Polydispersity-index(PDI),Zeta potential,encapsulation efficiency,stability,in vitro release,transmission electron microscopy,Fourier transform infrared spectroscopy,differential scanning calorimetry,and the ability to bind to albumin.The results showed that the particle size of ABD-Lip/Dex was 92.85 nm,and the PDI < 0.30 indicated a uniform degree of dispersion.The Zeta potential of-20.3 m V was conducive to the stability of liposomes,with the encapsulation efficiency of 80%.At 4℃ and37℃,there was no significant polymerization precipitation of ABD-Lip/Dex,indicating that the stability of this liposome was good.ABD-Lip/Dex could not release drugs rapidly,and it could prevent drug leakage to a certain extent,with good sustained-release effect.ABD-Lip/Dex was observed to be approximately spherical by transmission electron microscopy,and it was observed that ABD-LIP/DEX was regular and uniform in size.The results of Fourier transform infrared spectroscopy confirmed the successful coupling of ABD peptide with liposomes.The results of differential scanning calorimetry showed that the drug Dex existed in an amorphous phase,which might be dispersed inside the liposomes.The binding of ABD-Lip/Dex to albumin is much greater than that of Lip/Dex.Next,toxicity and uptake studies with ABD-Lip in Raw264.7 cells showed that Raw264.7 cells significantly increased uptake of ABD-Lip with little to no toxicity.Finally,the fluorescence distribution and anti-inflammatory effect of ABD-Lip in adjuvant-induced arthritis rats were studied systematically.The results of fluorescence distribution experiments in vivo showed that ABD-Lip/Di D had a good arthritis targeting effect after intravenous injection,and it could be detained at the inflammatory site for a long time.Anti-inflammatory results showed that ABD-Lip/Dex could effectively inhibit joint swelling and reduce the levels of inflammatory factors TNF-α and IL-1β in joint tissues.In summary,this paper prepared a liposome that can bind albumin in vivo.After intravenous injection,the liposome can actively target to the inflammatory site,increase the accumulation of drugs in the inflammatory site,and achieve the effect of effective treatment of rheumatoid arthritis,which can provide experimental basis and theoretical reference for the development of targeted drugs for rheumatoid arthritis. |
PDF Full Text Request