Glucose-responsive insulin delivery systems, which can maintain a stable level of blood glucose, have been proposed as a promising method to treat diabetes. Such systems can reduce potential toxicity and enhance patient compliance compared to traditional therapies. Accordingly, we designed a mesoporous silica nanoparticle (MSN)-based glucose-sensitive and self-regulated drug release system to achieve the goal of long circulation and "touch switch" in vivo. In this system, carboxyphenylboronic acid (CPBA) was first modified on the surface of MSN using amidation reaction. Insulin (INS) was then loaded in the channels of MSN (CPBA-MSN/INS) through physical adsorption, and sodium alginate (SA) was introduced onto the surface of the CPBA-MSN/INS nanoparticles as the gatekeeper via amidation reaction (SA/CPBA-MSN/INS). We found the drug loading capacity of INS was 261 mg/g. In the normal range of blood glucose, INS was scarcely released due to the reversible covalent interaction between 1,2-diols of SA and CPBA. Within the high concentration of glucose, the boronate esters could be dissociated, which results in the mesoporous channels opening and the release of INS. In vivo experiments on diabetic mice showed SA/CPBA-MSN/INS sustained a normal blood glucose level for up to 12 h with a single dose. Moreover, the lipid metabolism disorder and organ damage of diabetic mice were alleviated after treatment with SA/CPBA-MSN/INS. Therefore, SA/CPBA-MSN/INS characterized by an "on-off" regulated drug release property and high biosafety shows promise for applications in diabetes treatment.
Cubosomes with surface cross-linked chitosan exhibit anti-digestion effect, sustained drug release behavior, and significantly enhanced oral bioavailability of vinpocetine.
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