Papers of the Week

Most biologics require administration parenteral routes; however, the pain and local allergic reaction brought about by injection usually lead to poor compliance, especially for chronic patients. Meanwhile, the oral delivery of biologics faces great challenges due to the complex physiological environment of the gastrointestinal tract. Herein, we developed a new formulation of multilayer core-shell nanocapsules composed of hyaluronan-modified silica nanocapsules, chitosan and alginate layers for the oral delivery of biologics. The mesencephalic astrocyte-derived neurotrophic factor (MANF) was selected as the model biologic for the treatment of ulcerative colitis (UC). MANF-loaded biodegradable silica (MBS) nanocapsules were first obtained simultaneously with the preparation. Then, MBS nanocapsules were surface-modified with hyaluronan (MBSH) for oral targeted delivery to the inflamed region CD44-mediated endocytosis. To survive in the harsh gastrointestinal environment, MBSH was further modified using chitosan and alginate polyelectrolyte interactions. With this delivery system, , MBSH@CA, the cumulative release of MANF protein in the simulated gastric fluid (SGF) and simulated intestine fluid (SIF) was <10% of the total amount in MBSH@CA. Bio-distribution studies showed that the MBSH@CA nanocapsules were mainly distributed in the colon after 24 h treatment. imaging of the colons revealed a preferential accumulation of the MBSH@CA nanocapsules in the inflamed colons compared with the healthy colons. According to anti-inflammatory analysis, the oral MBSH@CA nanocapsules were effective in reducing related inflammatory symptoms caused by DSS-induced colitis. All of the above results suggested that the multilayer silica MBSH@CA nanocapsules could be employed for targeted drug delivery against UC.