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Abstract: TH-PO372

Kidney-Targeted Drug Delivery via Chitosan-Modified Liposome

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Xia, Ping, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Li, Wei, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Zhou, Yao, Xuzhou Medical University, Xuzhou, Jiangsu, China
  • Sun, Wei, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Gao, Kun, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
Background

Regarding kidney disease therapy, extra-renal effects, the inactivation of drug before reaching kidney or altered distribution due to the pathophysiology of diseases limit some medication widely use. The specific delivery or selective activation in kidney maximizes therapeutic effectiveness and minimizes toxic side effects. The improvement of the pharmacokinetic profile should be accomplished by drug targeting strategies. Liposome is single-layer or multi-layered vesicles composed of ordered lipid bilayers with an aqueous phase inside. Selective delivery of drugs in liposomes has been used clinically to treat some diseases because of their excellent biocompatibility, wide range of drug loading and low toxicity. They can increase the stability and solubility of the drug, give drug delivery and sustained release drug characteristics, and effectively improve the drug bioavailability. In this study, we evaluated the safety and effectiveness of chitosan-modified liposome as a kdiney-trageted delivery system.

Methods

To establish chitosan-modified liposome delivery system, liposomes were prepared by thin-film methods and post-insertion technology was performed to achieve chitosan modification. The morphology was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). To study the safety of this system, the cellular viability of human renal tubular epithelial cells, HK-2, was evaluated by cell proliferation kit. Drug release from the nanocomplex was analyzed at pH 7.4,6.8 and 5.0 using the dialysis method. To investigate the specific kidney-targeted delivery, the vector and its modified liposome was injected into mice and the distribution was analyzed by fluorescence imaging.

Results

Zeta potential of liposome pre- and post- chitosan modification confirmed the success of the reaction. The drug-loading system was spherical-like nanoparticles with an average particle size of (48.49±0.61) nm. The in vitro release results showed the nanoparticles had no burst release under physiological pH conditions. Near-infrared fluorescence imaging indicated that the system could be effectively distributed to the kidney. Furthermore, this system had no obvious toxicity to renal tubular epithelial cells.

Conclusion

The chitosan-modified liposome is expected to achieve renal targeted drug delivery and the drug-loading system is safe and stable.

Funding

  • Government Support - Non-U.S.