TABLE 3:
NP-Based Drug Delivery System Targeting the Inflamed Colon
| Nps Delivery System | Drug | Targeting Mechanism | Delivery Route | Colitis Model | Pros/Cons | Ref. |
|---|---|---|---|---|---|---|
| PLGA/Eudragit S100 NPs | Curcumin | pH-dependent | Oral | DSS mice | This delivery system significantly decreased neutrophil infiltration and TNF-α secretion while maintaining the colonic structure similar to the control group in a murine DSS-induced colitis model. | 46 |
| PLGA/Eudragit S100 NPs | Budesonide | pH-dependent | Oral | TNBS mice | The nanospheres loaded with Budesonide showed significant anti-inflammatory effects in the TNBS-induced colitis rat model. This therapeutic response could be related, first, to the higher drug levels that reached the colon and, second, to the specific adhesion and uptake of the nanospheres at the site of inflammation. | 47 |
| PLGA/Eudragit S100 NPs | Budesonide | pH-dependent | Oral | TNBS, DSS, and oxazolone mice | This nanoparticle delivery system may improve the anti-inflammatory efficacy of budesonide in terms of endoscopical, histological, and biochemical parameters in comparison with the free drug. Moreover, such nanoparticle delivery via oral administration can be further improved by implementing pH-sensitive release characteristics, eg, using appropriate coating. | 117 |
| ε‑polylysine-coated MSNs | prednisolone | pH-dependent | In vitro | RAW 264.7, LS 174T, and Caco-2 cell lines | This mesoporous silica nanoparticle (MSN) delivery system offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease. However, the authors only propose its use in vivo and did not show any in vivo data of colitis models. | 49 |
| PPADT/DOTAP NPs | TNF-α siRNA | ROS-responsive | Oral | DSS mice | Orally administered PPADT/DOTAP NPs loaded with siRNA against the proinflammatory cytokine TNF-α diminish TNF-α messenger RNA levels in the colon and protect mice from ulcerative colitis. This delivery system showed great potential for clinical application. | 54 |
| RNPo | TEMPOL or mesalamine | ROS-responsive | Oral | DSS mice | Orally administered RNPO accumulates specifically in the colons of mice with colitis and is more effective in reducing inflammation than low–molecular weight TEMPOL or mesalamine. RNPO might be developed for treatment of patients with ulcerative colitis. | 55 |
| MeO-PEG-b- PMOT block copolymer NPs | TEMPOL | ROS-responsive | Oral | DSS mice | Oral administration of RNPO did not change any composition of bacteria in feces, which strongly suggests a protective effect of RNPO on healthy environments in intestinal microflora. RNPO may become an effective and safe medication for treatment of UC. | 118 |
| Tpl/OxbCD NPs | TEMPOL | ROS-responsive | Oral | DSS and TNBS mice | Oral administration of Tpl/OxbCD NPs notably mitigated manifestations relevant to colitis and significantly suppressed expression of proinflammatory mediators. Accordingly, by scavenging multiple components of ROS, Tpl/OxbCD NPs may effectively reduce ulcerative colitis in mice and could be intensively developed as a translational nanomedicine for the management of IBD. | 57 |
| Chitosan-coated PLGA NPs | Lyophilized probiotic extract | Enzyme- responsive | Oral | TNBS rat | This nanoparticle-encapsulated form is very effective in the control of colitis. Regarding the safety of this compound, further studies should be conducted in patients with IBD. | 119 |
| PLA NPs | Tripeptide KPV | Hydrogel-based | Oral | DSS mice | By using NPs, KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy. Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD. | 61 |
| PEI/PLA NPs | CD98 siRNA | Hydrogel-based | Oral | DSS mice | This hydrogel-based delivery system showed therapeutic effect with colon-homing capabilities and the ability to directly release “molecularly specific” CD98 siRNA in colonic cells, thereby decreasing colitis. | 62 |
| TPP-PPM NPs | TNF-α siRNA | Mannose- mannose receptor | Ex vivo | DSS mice | This delivery system suggests that nontoxic TPP-PPM/siRNA NPs can be exploited as efficient, macrophage-targeted carriers for IBD therapy. However, the authors did not test its effect on this colitis model. | 69 |
| Mannosylated PLGA NPs | OVA | Mannose- mannose receptor | Oral | DSS mice | This delivery system only showed enhanced accumulation of OVA in inflamed colon tissue. | 68 |
| GTC/TPP NPs | Map4k4 siRNA | Galactose- galactose receptor | Oral | DSS mice | Oral administration of GTC/TPP NPs containing siMap4k4 significantly improved DSS-induced body weight loss, colon length shortening, and increase of myeloperoxidase activity. This study would provide an effective approach for oral siRNA delivery in the treatment of IBD. | 70 |
| PLGA NPs | CD98 siRNA and curcumin | HA-CD44 | Oral | DSS mice | This delivery system shows the promising capability of codelivered siCD98 and CUR for boosting conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy. | 71 |
| CD98 Ab-urocanic acid/ PEI NPs | CD98 siRNA | CD98 Ab-CD98 | Oral | DSS and CD4+CD45RBhigh T cell transfer mice | Nanoparticles containing surface CD98 antibody and loaded with siCD98 reduce expression of this protein by colonic epithelial cells and macrophages, and oral administration decreases the severity of colitis in mice. | 63 |
| F4/80 Ab-PLA- PEG NPs | TNF-α siRNA | F4/80 Ab- F4/80 | Oral | DSS mice | Fab’-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages. | 120 |
| Immunoliposomes | Transferrin-TfR | Ex vivo | DNBS rat | The results only showed that anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of nonspecific immunoliposomes, and there are no therapeutic results. | 75 | |
| Lectin-conjugated PLGA-NPs | Betamethasone | Lectin- lectin receptor | Oral | TNBS mice | Targeted NPs using lectins, especially with PNA, as stably targeting moiety in the GI tract seems to be a very promising tool in the future treatment of IBD. | 121 |
| Ultra-small solid archaeolipid NPs | Bexamethasone | TPA-scavenger receptors class A | In vitro | J774A1 cells | Because of their structural and pharmacodynamic features, SAN-Dex may be suitable for oral targeted delivery to inflamed mucosa. However, there are only in vitro results. | 122 |
| PLGA/PLA- PEG-FA NPs | 6-shogaol | FA-folate receptor | Oral | DSS mice | The results demonstrate a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating IBD. | 65 |