| Triptolide (TP), a highly oxygenated diterpene separated from Tripterygium wilfordii Hook. f. (TWHf) used in Chinese traditional medicine, is one of the main active component in TWHf. TP has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and significant anti-neoplastic activities. It can mainly treat more than fifty kind of diseases including rheumatoid arthritis, erythema nodosum, dermatomyositis, nephritis and reject reaction in organ transplant in clinics. However, its clinical application have largely been limited to some content due to its serious toxicity including gastrointestinal, urogenital, cardiovascular, blood circulatory system, bone marrow as well as hypersusceptibility of skin. In China, there are thousands of adverse events about TWHf or TP reported, especially in the gastrointestinal tract, such as mausea, vomiting, bellyache, diarrhea, duodenal ulcer, and gastrointestinal bleeding. So the incidence of adverse drug reaction (ADRs) was significantly higher than other drugs. Therefore, there is an important significance for the development of novel types of delivery systems in the clinical use of the drug. In present work, in order to alleviate the toxicity of TP or improve its activity, TP-loaded polymer nanoparticles (TP-PLA-NPs) have been prepared by using poly (D, L-lactide acid) as a carrier material due to its desirable biocompatible and biodegradable properties, particularly approved by Food and Drug Administration (FDA) for the clinic use. The main contents are as follows in this paper.1. TP-PLA-NPs were successfully prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method), which was selected on the base of particle size, polydispersity, appearance of the nanoparticle system and the precipitaion time. Meanwhile, some factors of effecting nanoparticle system were investigated in preparation process. The results obtained indicated that there was a more effect of surfactant concentration, polymer molecular, polymer concentration in organic solvent and the volume ratio of water to the oil phase on particle size, polydispersity index and encapsulation efficiency. In optimum conditions, the nanoparticles showed 149.7±21.5 nm of the particle size, 75 % of encapsulation efficiency, lower than 0.1 of polydispersity index. The morphology of nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion observed by transmission electron microscope (TEM), atomic force microscopy (AFM). 2. The physical states of drug and polymer material in nanoparticles were investigate fourier transform infra-red spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffractometry. The results obtained indicated that TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline and there were a weak interaction existed between the drug and polymer. The drug in vitro release from nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC) in the release experiment using dialysis bag diffusion technique. The results obtained exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. For the nanoparticles of 149.7 nm, the initial burst release was 11.45 % of the accumulative amount of TP released at the first sampling time of 0.5 h and 22.95 % of the accumulative amount of TP released within 24 h. In addition, we have investigated the effect factors of drug release from nanoparticles, for example, the particle size, the physical states of drug and morphology of nanoparticles.3. Anti-rheumatic inflammatory of TP-PLA-NPs was studied by using Freund's complete adjuvant (FCA) induced arthritis in rats by gavage. The results obtained indicated that TP-PLA-NPs had weak anti-inflammatory compared to TP for the same dosage at same time, but there was not significant difference among. The anti-inflammatory effect of TP-PLA-NPs gradually enhanced with the long taking time and exceeded t...
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