# Recent Advances in Nanoparticle-Mediated Treatment of Inflammatory Bowel Diseases
## 4 PH-Responsive Nanocarriers  
The therapeutic efficacy of glycyrrhizic acid encapsulated in pH-responsive nanocarriers was evaluated by [PERSON] et al., with results showing preferential targeting of the inflamed colon and mucosal healing. [13]. Modified double-emulsion method and solvent evaporation were employed for the preparation of Eudragit\({}^{\circledR}\)-S100 coated PLGA nanoparticles, with focus on their physical and chemical properties, chemical modifications of their surfaces, drug release kinetics, uptake and retention, and therapeutic efficiency. With sizes of about 200 nm, the nanoparticles exhibited excellent encapsulation efficiency, pH-dependent delivery using the Gompertz model. Antioxidant capacity assays, cytokine detection assays and macro/microscopic indices validated in vivo retention and therapeutic efficacy against inflamed colonic mucosa. The authors demonstrated that with the nanocomput they designed they achieved efficient colonic GA delivery and long-term mucosal healing. Preparation and evaluation of tacrolimus-loaded nanoparticles for topical application in IBD treatment was carried out in another study [14]. Simple oil in water (O/W) emulsion was used for the preparation of Eudragit P-4135F/PLGA nanoparticles. Both pH-responsive and polyester-based nanoparticles demonstrated their efficient role as anti-inflammatory agents in experimental colitis mouse models. In vivo studies were carried out on DSS-induced colitis mouse models identifying the likelihood of applying nanotechnology approaches. Benefits include decrease drug leakage and increased delivery of tacrolimus to the inflamed colon. PLGA nanoparticles determined higher drug concentrations to the site of inflammation, lower drug loading, and selective accumulation. On the one hand, there was a reduction in the clinical activity score and myeloperoxidase activity, and also there was an important increase in intestinal length following administration of all formulations containing tacrolimus. While both Eudragit P-4135F/PLGA nanoparticles proved to be efficient in reducing the inflammation, lower nephrotoxicity was observed in the case of pH-responsive nanoparticles [14]. In their study, [PERSON] et al. [15] assessed various methods to achieve more efficient colonic drug delivery for local or systemic drug effects and encapsulated ovalbumin (OVA) into (i) biodhesive N-Trimethyl chitosan (TMC) nanoparticles, (ii) pH-responsive Eudragit S100-based nanoparticles, and (iii) PLGA-based nanoparticles in order to achieve sustained drug release. These nanoparticles were analyzed in terms of size, zeta potential, drug entrapment efficiency and loading capacity. The horizontal diffusion chamber system was employed for ex vivo examination of the accumulation of these nanoparticles in inflamed colon tissue in mouse models. Ovalbumin was encapsulated into three different polymeric nanoparticles for colon targeted drug delivery. As pH-responsive nanoparticles exhibit controlled drug release, the drug is delivered specifically to the colon without being absorbed first in the upper GIT. With the purpose of penetrating the epithelial barrier and providing colon-specific drug release, in vitro findings suggest the use of TMC NPs as they appear to open the intercellular tight junctions and exhibit increased bioadhesion. Nevertheless, ex vivo examinations indicated that PLGA-PEG-Mannose nanoparticles show the highest accumulation of OVA in the inflamed colon, thus promoting the use of active targeting of immune-related cells in inflammation, with mannose playing an important role in targeted drug delivery to sites of inflammation. Being in agreement with the same approach, with the colon recognized as the preferred absorption site for the nanocarrier, the present study also focuses on the application of polymers used in nanoparticle drug delivery. An ideal carrier system for protein therapeutics should be designed to actively target macrophages and dendritic cells for a successful colonic delivery.