磁性核壳胶囊局域中和胃酸用于活性益生菌的高效递送

Magnetic Core/Shell-Capsules Locally Neutralize Gastric Acid for Efficient Delivery of Active Probiotics

近年来基于益生菌的幽门螺旋杆菌感染治疗策略受到了越来越多的关注,然而益生菌在胃部中直接递送会受到胃酸环境的干扰,难以存活,无法有效抑制幽门螺旋杆菌。为了实现益生菌在胃部的高效递送,我们制备了具有核壳结构的益生菌胶囊。胶囊外壳由海藻酸钙(Alg)、碳酸钙(CaCO_(3))以及铁钴磁性石墨纳米囊FeCo@G组成,胶囊内核为益生菌(约氏乳杆菌,Laj)菌液。其中,CaCO_(3)用于局域中和胃酸以保护内核益生菌,而FeCo@G则赋予了胶囊良好的磁驱动性能。我们利用扫描电子显微镜以及细胞显微成像系统等手段考察了益生菌胶囊的形貌和包裹稳定性,结果显示,胶囊能稳定包裹益生菌并抵御模拟胃液(SGF)中盐酸的侵蚀,维持了益生菌活性,并对幽门螺旋杆菌(H.p)具有明显抑制作用。此外,我们进一步探究了Alg/CaCO_(3)/FeCo@G-Laj(ACFL)胶囊在模拟胃部环境内的磁导航运动性能,结果表明,在磁场条件下,ACFL胶囊在不同粘度的介质中均可以实现高效的磁驱动效应,证实了ACFL胶囊的益生菌靶向递送能力。综上,ACFL胶囊为幽门螺旋杆菌的治疗提供新的方法,同时也为胃酸不稳定药物的高效保护以及精准投递提供了新平台。

In recent years,there has been significant interest in the potential of probiotics to inhibit the growth of Helicobacter pylori(H.pylori),a bacterium known to cause gastric infections.However,the effectiveness of probiotics in combating H.pylori is often hindered by their susceptibility to gastric acid,making it challenging for them to survive and remain active in the stomach.To address this issue,researchers have turned to hydrogel encapsulation as a promising strategy to protect probiotics.Therefore,we designed a hydrogelprobiotic capsules possessed both acid resistance and magnetic drive properties to protect and targeted-deliver probiotics in gastric conditions.The probiotic capsules with core-shell structure prepared by the electrostatic spray method can encapsule the probiotic without damaging the activity of probiotic.The probiotic capsule was composed of a calcium alginate/CaCO_(3)/FeCo@G(iron-cobalt magnetic graphitic nanocapsule) shell and a Laj(Lactobacillus Johnsonii,a kind of probiotics) core(Alg/CaCO_(3)/FeCo@G-Laj,ACFL).The capsules were thoroughly characterized using field emission scanning electron microscopy and cell microscopic imaging to verify their morphology and their ability to encapsulate probiotics.The results indicated that ACFL capsules maintained their integrity during a 2-h incubation in DPBS(Dulbecco's Phosphate-Buffered Saline) without releasing the probiotics,underscoring their robust encapsulation capacity.Moreover,ACFL could sustain the activity of Laj in SGF(simulated gastric fluid) for a long time by locally neutralizing the gastric acid through CaCO_(3).It's worth noting that Laj exhibits considerable H.pylori inhibition properties by secreting lactic acid to damage H.pylori and by competing adsorption for gastric epithelial cells with H.pylori.ACFL capsules demonstrated significant H.pylori inhibition properties even after exposure to SGF,further supporting the protective effect of the encapsulation strategy on probiotic activity.Moreover,in order to achieve efficient bactericidal performance in the real system,it is necessary to design a power device to give the capsule active propulsion ability to realize targeted delivery of Laj.FeCo@G,which possesses brilliant stability in acid environment on account of the protective graphitic shell,was integrated in ACFL for efficient magnetically navigated delivery.The results show that ACFL can reach a velocity of 3 cm·s^(-1) under the guidance of an external magnetic field,which confirms the ability of ACFL capsule to be potent tool for target delivery of probiotics.In conclusion,ACFL capsules hold promise for effectively targeting the gastric wall and releasing active probiotics to combat H.pylori infections.The combination of acid-neutralizing properties and magnetic navigation not only maintains the viability of the probiotics but also minimizes disruption to gastric homeostasis.This innovative approach offers a new avenue for protecting and controlling the release of active agents in the challenging gastric environment,opening up possibilities for improved treatments and interventions.