The Oral Drug Delivery System Study Of Curcumin-loaded Micro-and Nanoparticles For Ulcerative Colitis Therapy

Ulcerative colitis(UC),one of two types of inflammatory bowel disease(IBD),is a chronic inflammatory intestinal disease.Its etiology and pathogenesis is not completely clear.In the past few years,the incidence of UC is increasing sharply in our country.Due to its repeated episodes and low curative rate,UC is considered as a serious threat to the public health.Curcumin(CUR),a natural drug from the root of plant curcuma longa,has been received increasing attention as a promising drug for UC treatment due to its numerous merits,including anti-inflammatory,antioxidant,anticancer and hypolipidemic effect.Importantly,studies have shown that CUR is relatively safe for humans.However,its low solubility in aqueous solutions and low bioavailability limits its application.Micro-and nano-scale drug delivery system can offer a potential treatment strategy for UC.It can achieve improved solubility of poorly water-soluble drugs,extended the circulation time in body and sustained drug release,as well as enhanced targeting to inflammation sites.These benefits significantly reduce the side effect.In this paper,we designed a curcumin-loaded micro-or nanoparticles drug delivery system for the treatment of UC.The present research had two sections.In the first section,we prepared a series of pH sensitive microparticles(MPs)using poly(lactic-co-glycolic acid)(PLGA)and Eudragit S100(ERS100)as the drug delivery materials.The ratio of PLGA and ERS100 was set as 1:0,2:1,1:1,1:2 and 0:1,respectively.Accordlingly,these MPs were termed as MPs-1,MPs-2,MPs-3,MPs-4 and MPs-5,respectively.The pH sensitive MPs had a desirable particle size ranging from 1.52 to 1.91 μm.Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA,with some MPs exhibiting loading efficiencies over 80 %.Scanning electron microscopy(SEM)analysis showed that ERS100/PLGA MPs with a weight ratio of 1:2(MPs-4)can exist stably and degraded after the treatment of p H 7.2 phosphate buffer solution(PBS).In vivo,experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model,compared to free CUR.It was worth noting that pH sensitive MPs can maintain the stability of body weight and spleen weight,and reduce the myeloperoxidase(MPO)activity in mice.In the second section,CUR-loaded microparticles(CUR-MPs)and CUR-loaded nanoparticles(CUR-NPs)were prepared using PLGA by emulsion solvent evaporation method.We further characterized these particles from multiple aspects and compared the differences between CUR-MPs and CUR-NPs.The resultant spherical MPs and NPs exhibited slightly negative zeta-potential and had particle sizes around 1.7 μm and 270 nm,respectively.These particles had high encapsulation efficiency(over 50 %)and a desired drug loading capacity(3.5 % ? 7.0 %).The X-ray diffraction(XRD)analysis indicated that CUR had encapusulated into the particles.In release experiment,the drug cumulative release of CUR-MPs is only 15 %,while the cumulative release of CUR-NPs is about 50 %.Cell experiments exhibited that two types of particles had no obvious cytotoxicity and a strong anti-inflammation effect.In animal experiments,CUR-MPs and CUR-NPs had a certain treatment function to the DSS induced colitis model.Finally,we found that the therapeutic effect of CUR-NPs was superior to that of CUR-MPs in the aspects of body weight,spleen weight,length of colon and MPO activity.Collectively,MPs-4 had a superior therapeutic efficiency in alleviating UC.Further study showed the treatment effect of CUR-NPs is better than the CUR-MPs.