Synthesis, Characterization and In Vitro Evaluation of Triptolide-lysozyme Conjugate for Renal Targeting Delivery of Triptolide

다국어 초록 (Multilingual Abstract)

A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery
and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic
via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme.
The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it
a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS)
was confirmed by IR, 1H-NMR, MS and UV. The concentrations of triptolide in various samples
were determined by reversed-phase high-performance liquid chromatography (HPLC). In
this study, the physicochemical and stability profiles of TP-LZM under various conditions were
investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various
conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma
(less than 30 % of free triptolide released) and could release triptolide quickly in lysosome
(more than 80 % of free triptolide released) at 37oC for 24 h. In addition, the biological activities
of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested.
The conjugate can effectively reduce NO production in the medium of NRK52E induced by
lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to
promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

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