Oral Administration of Multistage Albumin Nanomedicine Depots (MANDs) for Targeted Efficient Alleviation of Chronic Inflammatory Diseases

Abstract

Methotrexate (MTX) by oral taking has been employed as the first‐line medication for various chronic inflammatory diseases treatment, such as Crohn's disease and rheumatoid arthritis (RA). However, the oral administration of MTX has very limited clinical benefits and will be discontinued due to the suboptimal response and severe adverse effects on intestinal mucosa. Herein, a multistage albumin nanomedicine depot (denoted as MAND) is formulated by encapsulating MTX‐loaded human serum albumin nanoparticles (MTX@HSA NPs) into calcium alginate chitosan microcapsules using a gas‐shearing technology. The MANDs can provide protection to MTX@HSA NPs with well‐persisted biologic activity against gastric acid erosion and realize specific boost release of MTX@HSA NPs in the intestinal tract in response to the mild basic circumstance. The MTX@HSA NPs absorbed by intestine can selectively accumulate in inflammation lesion by exploiting the inflammation targeting ability of HSA. In the animal experiments, the MANDs show improved therapeutic efficacy for the treatment of both RA and colitis with minimized intestinal side effects in respect to the free MTX by oral administration. Therefore, this conceived oral MANDs can promote a more clinic popularity and enhanced benefits of MTX for the treatment of chronic inflammatory diseases.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury

“…An additional peak at 3400 cm −1 was indicative of BSA protein's −OH absorption. 32,33 BSA•SH was confirmed for successful thiolation by a distinctive absorption peak at 2553 cm −1 . The presence of �C−H in the Mag structure was confirmed by a peak at 820 cm −1 .…”

Oral Nanomedicine: Challenges and Opportunities

“…For example, Zhang and co‐workers used calcium alginate‐chitosan complexes to encapsulate the anti‐inflammatory drug methotrexate (MTX)‐coated human serum albumin (HSA). [ 64 ] The calcium alginate hydrogel shell preserved the bioactivity of MTX@HSA NPs before it reached the intestine tissues. As a target protein, HSA can respond to the SPARC (Secreted protein, acidic and rich in cysteine) overexpressed in inflammatory lesion tissues, so that MTX medicines can be gradually adsorbed and accumulated in the lesioned intestine.…”

“…As a result, in mice with colitis and rats with rheumatoid arthritis models, this HSA‐based oral delivery platform ensured the security and effectiveness of MTX in the treatment of these chronic inflammatory diseases (Figure 5d). [ 64 ]…”

“…d) Schematic illustration of the preparation of MANDs. Adapted with permission [64]. Copyright 2023, Wiley-VCH.…”

Biomimetic Epigallocatechin Gallate–Cerium Assemblies for the Treatment of Rheumatoid Arthritis

“…Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease characterized by prolonged synovitis proliferation, progressive bone erosion, and cartilage destruction. − The exact pathogenesis of RA has not been fully elucidated, and it was demonstrated to associate with the fact that inflammatory cells infiltrate the synovial membrane and lead to severe destruction of articular cartilage. − Although the available drugs can improve symptoms and slow the progression of arthritis, at present, RA remains an incurable disease. Additionally, high doses and frequent administration are required to achieve satisfactory efficacy, which inevitably leads to adverse side effects. ,− Biological agents have also been developed to prevent joint destruction by inhibiting cytokine levels, but the treatment is less effective and comes with serious risks. , Obstacles to achieving effective treatment including the less accumulation of drug at joints and inadequate oxygen supply lead to the increase of reactive oxygen species (ROS) and inflammatory cytokines. − Therefore, the development of a novel therapeutic strategy enabling to target activated inflammatory cells and alleviate the inflammatory microenvironment of RA may be a promising direction.…”