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Rational design of oral drugs targeting mucosa delivery with gut organoid platforms

Bioactive Materials 2023年第12期30卷 116-128页

作者： Tianjian Tong Yijun Qi Derrick Rollins Luke D.Bussiere Debarpan Dhar Cathy L.Miller Chenxu Yu Qun Wang Department of Agricultural Biosystem and Engineering Iowa State UniversityAmesIAUSA Department of Chemical and Biological Engineering Iowa State UniversityAmesIAUSA Department of Veterinary Microbiology and Preventive Medicine College of Veterinary MedicineIowa State UniversityAmesIAUSA Interdepartmental Microbiology Program Iowa State UniversityAmesIAUSA Department of Statistics Iowa State UniversityAmesIAUSA

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads(i.e.,immunogens)against gastric *** this study,hollowed nanocarriers(NCs:silica nanospheres and gold nanocages)with poly-l-lysine(PLL)coating and mammalian orthoreovirus cell attachment proteinσ1 functionalization(NC-PLL-σ1)were explored as functional oral drug delivery vehicles(ODDVs).The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells(M-cells)mediated transcytosis(viaσ1-α2–3-linked sialic acids adherence)across gastrointestinal *** coating provided protection and slow-release of rhodamine 6 G(R6G),a model *** transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in *** compared with other experimental groups,the fully functionalized ODDV system(with PLL-σ1)demonstrated two significant advantages:a significantly higher transport efficiency(198%over blank control at 48 h);and protection of payloads which led to both better transport efficiency and extended-release of payloads(61%over uncoated carriers at 48 h).In addition,it was shown that the M cell presence in intestinal organoid monolayers(modulated by Rank L stimulation)was a determining factor on the transport efficiency of the ODDVs:more M-cells(induced by higher Rank L)in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload(R6G).The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.

关键词： Oral drug delivery vehicles Organoids Biomimetic virus sigma 1 protein Gold and silica nanoparticles

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