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Study on Peptide Fragment of Human Serum Albumin as a Novel Renal Targeting Drug Carrier

Author: HeXiaKai
Tutor: XuChaoQun
School: Chengdu University of Traditional Chinese Medicine
Course: Pharmacy
Keywords: human serum albumin peptide fragments renal targeting drug carrier optical imaging in vivo cytotoxicity cellular uptake
CLC: R943
Type: Master's thesis
Year: 2013
Downloads: 6
Quote: 0
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Abstract


Selective targeting of drugs to kidneys may enable an increased renal effectiveness combined with a reduction of extrarenal toxicity. Some reports at home and abroad showed that many carriers exhibited the fine renal targeting profiles, including lysozyme, low molecular weight chitosan, glycosyl compound and poly(vinylpyrrolidone-co-dimethyl maleic acid)(PVD). However, the problems of poor biocompatibility and safety of materials themselves as the obstacles were not resolved yet, which caused that there has been no renal targeting carrier for intravenous injection used in clinical therapy until now on. In addition, domestic research on renal targeting was a weak link of drug delivery field and only a few of research paper about renal targeting carrier were reported. Therefore, these problems seriously hamper the development of renal delivery system.To develop the proper renal targeting carrier for clinical therapy, human serum albumin, as starting material, was firstly cleaved into albumin fragments and Superdex15was used to separate and purify the degradation products. Then, the carboxymethylcellulose (CM-Sepharose FF) was used for further separation and purification. Consequently, three peptide fragments (PF) with certain sequence were obtained as candidates of renal targeting carrier, which were named PF-A1-123, PF-A124-298and PF-A299-585.Then, Hela and MDCK cell were respectively used to investigate the cytotoxicity of three PFs and the results demonstrated three PFs had no adverse effects on the Hela and MDCK cell in the concentration range from0.05mg·ml-1to5.00mg·ml-1. After that, cellular uptake of MDCK was studied preliminarily to explore the cellular uptake rate of three PFs. Fluorescein isothiocyanate (FITC) trace methods were applied with taking fluorescence intensity as index to screen the PF which had the highest cellular uptake rate. The results showed that PF-A299-585was uptaken more than PF-A1-123and PF-A124-298.Finally, optical imaging in vivo and FITC trace methods were utilized to explore the renal targeting profiles of three PFs to further screen the optimal fragment and the result showed that PF-A299-585possessed the best renal targeting effect. Meanwhile, using fluorescence imaging, we found for the first time that PFs of human serum albumin selectively accumulated in the kidneys, especially in the renal tubules after i.v. injection in mice. Therefore, PF-A299-585was selected as the optimal renal targeting carrier according to the in vivo behavior and cytological studies, which can supply available information to research the specific renal uptake of PFs of human serum albumin and develop renal delivery system for clinical therapy.

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