# Recent Advances in Nanoparticle-Mediated Treatment of Inflammatory Bowel Diseases
## 2 Budesonide Loaded Nanoparticles  
IBD represents a global health issue with North America, specifically the USA, making a prominent contribution to the global number of patients with IBD. Topical steroids such as enema formulations of micronized budesonide are a sustainable treatment for distal colitis. However, [PERSON] et al. [3] consider it too large to be effective in penetrating the colonic mucus and suggest the use of budesonide nanosuspension (NS) with an appropriate coating and size to ensure better permeation. They showed that 200 nm muco-inert fluorescent polystyrene particles coated with Pluronic F127 achieved enhanced mucus penetration in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD in mice as compared to 2 \(\upmu\)m polystyrene particles coated with polyvinylpyrrolidone (PVP), the stabilizer used in the clinical micronized budesonide formulation. The wet-milling process was further used to prepare \(\sim\)230 nm budesonide NS coated with muco-inert Pluronic F127 and \(\sim\)2 \(\upmu\)m PVP-capped budesonide microsuspension. The conjugate was delivered in a mouse model of TNBS-induced IBD. Results showed that daily therapy with budesonide NS enema significantly decreased colon weight and histology scores when compared to no-treatment controls or mice under daily budesonide MS therapy [3]. Budesonide-loaded nanoparticles with pH-sensitive coating were prepared by [PERSON] et al. [4] to treat ulcerative colitis. The developed nanobiosystems were observed by transmission electron microscopy, assessing their size, drug load and encapsulation ability. The pharmacokinetics and pharmacodynamics of drug-release behavior was evaluated in vitro. The rat colitis model was induced by TNBS. Diffusion dynamics of nanoparticles displayed an average 110.5 size in nm and a polydispersity index of 0.098 for the eutdragitS100-coated budesonide-loaded poly (lactic-co-glycolic) acid (PLGA) NPs. Transmission electron microscopy (TEM) images confirmed the circular shape and regular size of the conjugates. They also exhibited minimal drug release in the stomach and the small bowel with maximal release in the colon. Pharmacodynamics showed that the concentration of myeloperoxidase (MPO) in the conjugates was similar to that of the control group. Pathological examination of rectum specimens indicated the absence of necrotic or disrupted epithelial cells [4]. The preparation of nanospheres as drug delivery systems to specifically target the inflamed colon in UC [5] incorporated both the unique properties of pH-responsive polymers and the target-specific controlled-release biodegradable polymers. The matrix-type nanosystems combined PLGA with a pH-responsive methacrylate copolymer in order to slow down premature drug release in the small intestine, to control drug release in the distal part of the gastrointestinal tract, and to achieve colon-specific targeted delivery of drug-loaded NPs. The pH-responsive nanospheres were loaded with budesonide due to the high first-pass metabolism with minimal systemic absorption of the corticosteroid. The evaluation of in vivo therapeutic efficacy of the novel nanospheres was done by comparing it with conventional drug-loaded enteric microparticles in a rat model of trinitrobenzenesulfonic acid(TNBS)-induced colitis. Importantly, the release profile of the drug (PLGA/Eudragit nanospheres--1:1 \(w/w\)) displayed a decrease in premature drug release before reaching its site of action, which represents a common issue in the case of pH-dependent systems. Moreover, the initial burst release of PLGA NPs might be reduced when loading nanospheres with Eudragit S100 [5]. In another study, budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules were prepared for colon-drug delivery by [PERSON] et al. [6] Nanoprecipitation was used for the preparation of the nanocapsules, which consisted of a pH-sensitive Eudragit S 100 polymer and propylene glycol monocaprylate (Capryol 90) [6].