# Recent Advances in Nanoparticle-Mediated Treatment of Inflammatory Bowel Diseases
## 4 PH-Responsive Nanocarriers
The O/W single emulsion method was used to develop a new pH-responsive nanocomposite for colon-specific drug delivery. The authors intended to reduce premature drug delivery in the stomach and obtain gradual and continuous release in the distal part of the GIT following oral administration [16] (Figure 2). The main focus was on the effects budesonide had on the uptake of glucose in the intestinal mucosa of mice with IBD. The authors created a drug to test the significant local anti-inflammatory effects of the glucocorticoid loaded in core-shell PLGA composites and coated with Eudragit S100. Budesonide undergoes extensive presystemic biotransformation via cytochrome P450 and only a very small percentage of the dose is absorbed into the systemic circulation during passage. Therefore, the need for a carrier used for the local delivery of the drug. The authors prepared budesonide-loaded PLGA NPs with and without enteric coating using the same approach and studied their therapeutic efficacy in TNBS-induced colitis, DSS colitis, oxazolone colitis in mouse models. They compared the results with budesonide alone and plain PLGA NPs. Their outcome showed an enhanced budesonide efficacy for nanoparticles in contrast to budesonide alone based on endoscopic, histological and biochemical assessments [16] (Figure 3). Figure 2: (**A**) In vivo high resolution mini-endoscopy of mice intestine after treatment. (**B**) Colitis score of all the three different animal models after treatment with free budesonide and budesonide-loaded nanoparticles in comparison with the inflamed group. (**C**) Pooled data of all untreated and treated groups for statistical significance Reprinted with permission from [16]. PLGA/Eudragit S100 NPs were tested for the local delivery of curcumin in the treatment of IBD [17]. Curcumin-loaded nanoparticles were assessed both in vitro, showing the secretion of lower levels of pro-inflammatory cytokines, namely TNF-alpha, by activated macrophages (J774 cells) and observing the transport of curcumin in Caco-2 cell monolayers, and in vivo. Using a mouse model of colitis employing DSS, the authors observed that following administration, the infiltration of neutrophils was decreased and lower plasma levels of tumor necrosis factor alpha were observed. Excised colons were used for histological evaluation of inflammation and for the determination of the presence of curcumin (CC)-loaded nanoparticles. CC-loaded nanoparticles were analyzed in comparison to curcumin in suspension, both in vitro and in vivo, for colon-specific delivery for the treatment of IBD. When encapsulated, curcumin showed increased permeability through the intestinal barrier in vitro when compared to suspension, determining an improvement in the permeability of curcumin across Caco-2 cell monolayers. CC-loaded nanoparticles also reduced tumor necrosis factor-\(\alpha\) secretion to a greater extent in macrophages activated after LPS treatment. In vivo measurements showed that the activity of the highly oxidative enzyme MPO, as well as the secretion of tumor necrosis factor-alpha, was lower in DSS-colitis mice treated with curcumin-loaded nanoparticles. There was evidence of colon targeted delivery of curcumin 12 h following nanoparticle administration [17]. Figure 3: **(A)** In vivo myeloperoxidase (MPO) activity measurement in live mice by luminescence detection. **(a)** inflamed colitis as control, **(b)** free budesonide treated **(c)** treated with budesonide loaded plain nanoparticles, **(d)** treated with budesonide loaded coated nanoparticles. **(B)** Cryosectional study by immunohistochemical technique where the coated nanoparticles showed low extent of granulocytes. Reprinted with permission from [16]. The efficacy of ursodeoxycholic acid nanoparticles was tested in animal models of IBD [18]. Eudragit RS 100 and RL 100 nanoparticles demonstrated continuous release of ursodeoxycholic acid in vitro, with enhanced efficacy in vivo in comparison to ursodeoxycholic acid UDCA alone, preventing the ulcer from extending.