Multiple drug resistance (MDR) in bacterial infections is developed with the abuse of antibiotics, posing a severe threat to global health. Tedizolid phosphate (TR-701) is an efficient prodrug of tedizolid (TR-700) against gram-positive bacteria, including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). Herein, a novel drug delivery system: Red blood cell membrane (RBCM) coated TR-701-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles (RBCM-PLGA-TR-701NPs, RPTR-701Ns) was proposed. The RPTR-701Ns possessed a double-layer core-shell structure with 192.50 ± 5.85 nm in size, an average encapsulation efficiency of 36.63% and a 48 h-sustained release in vitro. Superior bio-compatibility was confirmed with red blood cells (RBCs) and HEK 293 cells. Due to the RBCM coating, RPTR-701Ns on one hand significantly reduced phagocytosis by RAW 264.7 cells as compared to PTR-701Ns, showing an immune escape effect. On the other hand, RPTR-701Ns had an advanced exotoxins neutralization ability, which helped reduce the damage of MRSA exotoxins to RBCs by 17.13%. Furthermore, excellent in vivo bacteria elimination and promoted wound healing were observed of RPTR-701Ns with a MRSA-infected mice model without causing toxicity. In summary, the novel delivery system provides a synergistic antibacterial treatment of both sustained release and bacterial toxins absorption, facilitating the incorporation of TR-701 into modern nanotechnology.
Chitosan and its derivatives have been increasingly used for bacteriostasis. To date, the effect of chitosan and N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) on Enterococcus faecalis (E. faecalis) associated with endodontic infection has remained to be determined. Chitosan and HTCC were serially diluted with double-distilled water (DDW) or PBS at concentrations of 20-2,500 µg/ml. Various strains of E. faecalis (American Type Tissue Collection no. 29212, as well as isolated strains P25RC and P52Sa) in plankton were adjusted to an optical density at 600 nm of 0.10 and treated with chitosan or HTCC. A colony-forming unit assay was used to determine the concentration of residual bacteria after treatment. Furthermore, E. faecalis biofilms were cultured on coverslips and treated with chitosan or HTCC. The coverslips were rinsed, stained using Live/dead ® BacLight™ bacterial viability kit and observed under an inverted fluorescence microscope. In addition, biofilms on dentine blocks were prepared and observed under a scanning electron microscope. MC3T3-E1 pre-osteoblasts were seeded on 96-well plates and treated with chitosan or HTCC at various concentrations. The cytotoxicity of chitosan and HTCC on MC3T3-E1 pre-osteoblasts was detected using a Cell Counting Kit-8 assay after 24, 48 and 72 h of treatment. The results revealed that the final minimum bactericidal concentrations (MBC) of chitosan and HTCC dissolved in DDW were 70 and 140 µg/ml, respectively. Chitosan and HTCC in DDW exerted a significantly greater antibacterial effect as compared with that in PBS (P<0.05). At the MBC, chitosan and HTCC in DDW, but particularly chitosan, had a significant antibacterial effect on E. faecalis biofilm. Chitosan exhibited no cytotoxicity to MC3T3-E1 pre-osteoblasts at a concentration of <625 µg/ml, while HTCC inhibited the proliferation of the cells in the concentration range of 39-10,000 µg/ml. In conclusion, chitosan and HTCC exhibited prominent antibacterial properties on E. faecalis in the planktonic state and as a biofilm via charge interaction, indicating their potential for application in root canal disinfection and fillings.
Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short halflife and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. From in vitro evaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na þ /K þ-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. For in vivo evaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.
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