Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.
Administration, Cutaneous ; Diterpenes ; Drug Delivery Systems ; Epoxy Compounds ; Needles ; Phenanthrenes ; Skin

OBJECTIVETo screen the formulations of cryptotanshinone gel for treatment of topical diseases such as acne.

METHODDifferent cryptotanshinone gels incorporating various penetration enhancers at different concentrations were prepared using carbopol 934L as matrix. The steady transdermal fluxes and drug retention amounts in skin of the gels were investigated on single chamber diffusion cells using excised rat abdomen skin as model and 40% polyethylene glycol-400 saline as releasing media. The optimal formulation would be the gel which had the maximum drug retention amount/ transdermal drug flux ratio.

RESULTThe promotion effects of menthol at different concentrations were as follows: 5% > 3% > 1%, and the effects on drug retention amount in skin were followed as: 5% approximately equal 3% > 1%; The promotion effects of a zone at different concentrations were as follows: 5% approximately equal 3% > 1%, and the effects on drug retention amount in skin were as follows: 5% > 3% approximately equal 1%. Combination of enhancers showed no superior effects compared to single uses. 5% azone had the maximum retention amount/ transdermal flux ratio.

CONCLUSIONThe optimal formulation was the cryptotanshinone gel containing 5% azone.

Administration, Topical ; Animals ; Chemistry, Pharmaceutical ; Gels ; Male ; Permeability ; Phenanthrenes ; administration & dosage ; chemistry ; metabolism ; Rats ; Rats, Sprague-Dawley ; Skin ; metabolism

OBJECTIVETo develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.

METHODSTriptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.

RESULTSTriptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.

CONCLUSIONTriptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cyclodextrins ; Diterpenes ; administration & dosage ; pharmacology ; Drug Carriers ; Epoxy Compounds ; administration & dosage ; pharmacology ; Humans ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyethyleneimine ; Polymers

OBJECTIVETo explore clinical features the adverse reactions of Tanshinone II(A) Sodium Sulfonate Injection (T II(A) SSI) and their reasons, thus providing reference for rational medication.

METHODSThe literatures on adverse reactions and incompatibilities of T II(A) SSI were retrieved (domestic medical journals from January 2000 to December 2011) and statistically analyzed.

RESULTSIn the 18 cases of adverse drug reaction (ADR), the clinical manifestations of T II(A) SSI induced adverse reactions were various, involving reactions of appendages and the neuromuscular system (each accounting for 50%). The elderly and women were mainly involved. Many organs and systems were involved. There existed more incompatibilities.

CONCLUSIONThe medical workers should pay special attention to T II(A) SSI induced adverse reactions, thus avoiding recurrence of ADR, evading risks, and ensuring safe and rational medication.

Adult ; Aged ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Injections ; Male ; Middle Aged ; Phenanthrenes ; administration & dosage ; adverse effects

Animals ; Coronary Restenosis ; prevention & control ; Diterpenes ; administration & dosage ; Epoxy Compounds ; Iliac Artery ; pathology ; Male ; Phenanthrenes ; administration & dosage ; Rabbits ; Stents ; Tunica Intima ; pathology

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.
Animals ; Anthelmintics/*administration & dosage ; Disease Models, Animal ; Drug Synergism ; Female ; Humans ; Intestines/parasitology ; Ketoconazole/*administration & dosage ; Liver/parasitology/pathology ; Male ; Mice ; Parasite Load ; Phenanthrenes/*administration & dosage ; Quinine/*administration & dosage ; Schistosoma mansoni/isolation & purification ; Schistosomiasis mansoni/*drug therapy/pathology ; Treatment Outcome

Tanshinone IIA nanoparticles were constructed and perfused in rabbit's right carotid after intimal denudation with ballon. Localization and retention at different time points of the coumarin-labeled drug nanoparticles were evaluated under laser confocal microscope. Nanoparticles were seen in the three layers of the cross-section artery. At 7 days, they were mainly deposited in the medial layer, while the deposition was generally observed in the adventitia and media at 14 days and 28 days. In the Tanshinone IIA nanoparticle study, a significant reduction of the neo-intimal hyperplasia was noted by comparing the intimal area and the intima-media ratio in the three groups. And the PLGA nanoparticles appeared to be fully biocompatible. As a result, the local administration of the nanoparticles with incorporated Tanshinone IIA showed not only the preventive effects, but aslo the high absorption and good biocompatability in the whole arterial wall.
Angioplasty, Balloon ; adverse effects ; Animals ; Caprolactam ; administration & dosage ; analogs & derivatives ; Carotid Arteries ; pathology ; Diterpenes, Abietane ; Drug Carriers ; Hyperplasia ; etiology ; prevention & control ; Lactic Acid ; administration & dosage ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyesters ; Polymers ; administration & dosage ; Rabbits ; Tunica Intima ; drug effects ; pathology

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.
Androgens ; blood ; Animals ; Diterpenes ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Epoxy Compounds ; administration & dosage ; Humans ; Male ; Phenanthrenes ; administration & dosage ; Prostate ; drug effects ; growth & development ; Prostatic Hyperplasia ; blood ; drug therapy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood ; Tripterygium ; chemistry

OBJECTIVETo develop a HPLC method for determination of triptolide in tripterygium total terpenoids tablets.

METHODA Lichrospher CN column was used with ethanol and water for gradient elution. The detection wavelength was set at 255 nm.

RESULTThe linear relationship of the concentrations and peak areas was good in range of 0.742-59.4 microg x mL(-1) (r = 0.9998). The average recovery was 99.2%, RSD% = 1.7%.

CONCLUSIONThe method is simple, rapid and accurate and can be used for quality control of the tablets.

Chromatography, High Pressure Liquid ; methods ; Diterpenes ; analysis ; Epoxy Compounds ; Phenanthrenes ; analysis ; Plants, Medicinal ; chemistry ; Quality Control ; Tablets ; Terpenes ; administration & dosage ; chemistry ; isolation & purification ; Tripterygium ; chemistry

OBJECTIVETo prepare and evaluate an intravenous emulsion of tanshinone II(A).

METHODSoybean phospholipid mixing with poloxamer 188 was used as emulsifier. Oleic acid and glycerol were used as co-emulsifier and isoosmotic adjusting agent, respectively. The coarse emulsion was first prepared and following homogenization was carried out for the coarse emulsion by using a high pressure homogenizer.

RESULTThe average diameter of the prepared tanshinone II (A) emulsion was 211 nm with a zeta potential of -32. 1 mV. There had no changes of diameter, zeta potential, pH value, content and physical appearance for the tanshinone II (A) emulsion stored at 25 degrees C away from light during one year.

CONCLUSIONThe physicochemical properties of the prepared tanshinone II (A) emulsion was stable, which could meet the requirements of intravenous administration.

Centrifugation ; Diterpenes, Abietane ; Drug Stability ; Drug Storage ; Emulsions ; Hydrogen-Ion Concentration ; Injections, Intravenous ; Particle Size ; Phenanthrenes ; administration & dosage ; chemistry ; Quality Control ; Temperature