Preparation, characterization, and Staphylococcus aureus biofilm elimination effect of baicalein-loaded tyrosine/hyaluronic acid/ß-cyclodextrin-grafted chitosan nano-delivery system.

Staphylococcus aureus (S. aureus) is an important cause of infections associated with implanted medical devices due to the formation of bacterial biofilm, which can prevent the penetration of drugs, thus posing a serious multi-drug resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is one of them. In order to enhance the biofilm elimination effect of Baicalein (BA), a BA-loaded Tyr/HA/CD-CS nano-delivery system was successfully prepared using ß-cyclodextrin grafted with chitosan (CD-CS), Hyaluronic Acid (HA), and D-Tyrosine (D-Tyr). The Tyr/HA/CD-CS-BA-NPs have a uniform particle size distribution with a particle size of 238.1 ± 3.06 nm and a PDI of 0.130 ± 0.02. The NPs showed an obvious inhibitory effect on planktonic bacteria with a MIC of 12.5 µg/mL. In vivo and in vitro tests showed that the NPs could enhance the elimination effect of BA on the MRSA biofilm. The results of Confocal Laser Scanning Microscopy (CLSM), Live & Dead Kit, and colony count experiments illustrated that Tyr/HA/CD-CS-BA-NPs could enhance the permeability of drugs to the biofilm and improve the ability to kill the biofilm bacteria, which may be an important mechanism to enhance the elimination of the MRSA biofilm. These findings will help develop new, effective medicaments for treating bacterial biofilm infections.

Release profile of insulin from pH-sensitive hydrogel and its hypoglycemic effect by oral administration.

The purpose of this study was to investigate the release profile and in vivo hypoglycemic effect of insulin (INS)-loaded pH-sensitive hydrogel (INS-TPM950) administrated by oral route. TPM950 was fabricated via a free polymerization method and its inner morphology was observed with a scanning electron microscope (SEM). INS was encapsulated into TPM950 by an adsorption method, and the in vitro release profiles of INS from INS-TPM950 were revealed in pH 1.2 and 6.8. To investigate the hypoglycemic effect of INS-TPM950, Male Wistar rats were used in modeling of diabetes mellitus by multiple intraperitoneal injection of alloxan. The in vivo hypoglycemic effect of oral INS-TPM950 was studied, and the optimal dosage was also determined. SEM photograph showed that abundant 3D meshes were distributed in the inner of TPM950 hydrogel. INS release profile suggested that only 18.2 ± 11.3% INS was released in pH 1.2, but over 88.8 ± 4.9% was delivered into phosphate buffer solution in pH 6.8. After injection to the diabetic rats, the released INS solution from INS-TPM950 exhibited an obvious hypoglycemic effect. Oral administration of 50.0 I.U./kg of INS-TPM950 showed a slow but effective hypoglycemic effect, and the lowest blood glucose level was reached to 47.5 ± 5.5% of the original level. Therefore, this formulation had a potential application in diabetes treatment via oral ingestion.