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The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.
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The non-specific administration of antitumor drugs is the main cause for the side effects of chemotherapy drugs on normal tissues. The application of nanotechnology in the delivery of anti-tumor drugs is one of the important ways to improve the therapeutic effect and to reduce the side effects. The current study aimed to synthesize pH responsive poly (methoxy-ethylene glycol)-poly(lactic acid)-poly-(β-amino ester) (PBAE) triblock copolymers to deliver docetaxel (DTX) and improve the anti-tumor activity of DTX. PBAE was synthesized by ring opening polymerization and Michael addition reaction, its structure and molecular weight was characterized by 1H NMR, the dissociation constant of base (pKb) were determined by acid-base titration method. The critical micelles concentration (CMC) of copolymers was measured by pyrene fluorescence spectroscopy. DTX loaded copolymer micelles were prepared by membrane hydration method. The size and its distribution as well as the stability of micelles were determined by laser light scattering analysis. The drug loading content (DL), entrapment efficiency (EE) and cumulative drug release from micelles were evaluated by high-performance liquid chromatography (HPLC). The sizes of DTX drug-loaded micelles were in the range of 10 to 100 nm with narrow distribution. DL of DTX in PBAE1 and PBAE2 micelles was (5.3 ± 0.10) % and (4.9 ± 0.05) %, respectively, with EE was (93.8 ± 1.70) % and (87.2 ± 4.10) %, respectively. The drug-loaded micelles showed pH sensitive drug release properties under weak acidic conditions, which showed potential drug release of DTX under mild acidic tumor environment. A mouse Lewis lung carcinoma model was established to evaluate the therapeutic efficacy of micellar DTX formulations. Significant inhibitory effect of the nanodrugs was observed with DTX dosages of 10 and 20 mg·kg-1, respectively. Moreover, the pH responsive PBAE1-DTX micellar drug exhibited stronger therapeutic efficacy on mice xenograft tumor, as compared with the non pH sensitive micellar drug (PELA-DTX) and free DTX. All animal experiments were performed according to the animal ethical standards and approved by the Animal Experiments and Ethical Committee of China Academy of Chinese Medical Sciences (No. 2017090110). The in vivo anti-tumor activity studies showed that the tumor volume growth rates of mice in different drug-administered groups were: PBAE1-DTX 20 mg·kg-1 < PBAE1-DTX 10 mg·kg-1 < PELA-DTX 10 mg·kg-1 < DTX 10 mg·kg-1 < normal saline, with the PBAE1-DTX group as the most potent group for tumor inhibition. The current pH sensitive DTX nano-micelles showed high potential in further studies to promote the application of nano DTX formulations for tumor treatment.
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Objective: To study the secondary metabolites of endophytic fungus Aspergillus fumigatus from Euphorbia royleana. Methods: The fermentation liquor of the fungal strain A. fumigatus was isolated and purified using various chromatographic methods. The structures of the compounds were identified by spectroscopic analysis. Results: Three compounds were isolated and their structures were identified as (R)-2-propylhexyl-2H-1,2,3-triazole-4-carboxylate (1), decumbenone A (2), and (+)-cyclopenol (3). Conclusion: Compound 1 is a new compound isolated from this fungus, which is identified as aspergillus triazolate A.
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Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.
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China is highly rich of medicinal plants. Traditional Chinese medicine(TCM) has a long history and is important traditional resources in China. As one of the important strategic resources and the link among all the countries along the ancient "Silk Road", TCM has played important role in economy, politics, society and ecology. With the initiative of the "Belt and Road" in recent years, many natural resources of TCM now are facing the risk of extinction due to more and more frequent trade between China and other countries, also the increase of export has influenced to the stock of TCM. In order to prevent the loss of the resources, strengthen the protection and sustainable use of TCM, our study provided the strategies to the natural resources of TCM's entry-exit supervision from nine aspects, like law and regulation system, based on the analysis of current supervision status quo.
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China , Conservation of Natural Resources , Drugs, Chinese Herbal , Ecology , Medicine, Chinese Traditional , Plants, MedicinalABSTRACT
Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
Subject(s)
Animals , Mice , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Docetaxel , Pharmacology , Drug Carriers , Lung Neoplasms , Drug Therapy , Pathology , Micelles , Nanoparticles , Particle Size , TaxoidsABSTRACT
Objective To perform a preformulation study for a new antirheumatic drug DK-507 so as to provide theoretical basis for its preparation research.Methods The appearance,crystal form and solubility of DK-507 were investigated.A high perfor-mance liquid chromatography(HPLC)method for the quantitative determination of DK-507 was established.The apparent oil/water (O/W)partition coefficient of DK-507 and the equilibrium solubility of the drug under different pH conditions were determined. Re-sults DK-507 is a white crystalline powder,which is odorless,tasteless and insoluble in water.The quantitative HPLC method for the DK-507 determination showed a good linearity in the range of 10-80 μg/ml(R=0.9998).The apparent O/W partition coefficient of DK-507 was determined to be 1.80.In the different pH solutions,the solubility of DK-507 showed a W-form change,with poor solubili-ties in lower pH solutions,which showed a gradient improvement with the increase of the solution pH values.Conclusion The quanti-tative HPLC method for the DK-507 determination,established in this study,is accurate and reliable.The present results indicate that DK-507 is a water-insoluble drug,and according to the O/W partition coefficient,DK-507 seems likely to be prepared into oral solid preparations.
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Objective To study the physical-chemical parameters of antiviral drug GZ 914 and provide data for the preparation design .Methods The appearance , crystal structure and solubility of GZ 914 were investigated .An HPLC method was established to determine the content of GZ 914 in vitro before oil/water partition coefficient and solubility in different pH experiments were calculated .Results GZ914 was a straw yellow powder with a crystalline structure , low water-solubility and good lipotropy .The HPLC method had a good linear relationship within the range of 12-60 μg/ml (r=0.9998).The oil/water partition coefficient of GZ914 was 1.9.Conclusion This analytical method is accurate and reliable.The oil/water partition coefficient indicates that the drug could be formulated as an oral solid preparation.
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To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3β-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3β, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3β-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3β, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC₅₀>50 mg•L⁻¹).
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<p><b>OBJECTIVE</b>To investigate the value of five-repetition sit-to-stand test (5STS) in clinical evaluation of elderly patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Fifty-one patients with COPD and 20 healthy individuals were enrolled in this study. All the participants underwent 5STS, pulmonary function examination, and 6 min walking test (6MWT) and were evaluated for severity of dyspnea (by mMRC) and BODE index during the tests.</p><p><b>RESULTS</b>All the participants completed 5STS test with a good reproducibility of the time used for 3 sessions of the test (P<0.001). The mean time used by COPD patients for 5STS was significantly longer than that by healthy individuals (12.93±3.11s vs 0.72±0.71 s, P=0.002). The results of 5STS showed a significant negative correlation with those of 6MWT in the case group and control group with correlation coefficients of -0.611 and -0.682, respectively. The results of 5STS were negatively correlated with FEV1%Pre and body mass index (P<0.05) but positively with mMRC and BODE index in COPD patients (P<0.05).</p><p><b>CONCLUSION</b>5STS is a simple and reproducible test to evaluate the patients' exercise capacity and the severity of COPD, and is well correlated with the current methods for clinical evaluation of COPD.</p>
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Humans , Body Mass Index , Case-Control Studies , Dyspnea , Exercise Test , Pulmonary Disease, Chronic Obstructive , Diagnosis , Reproducibility of Results , Respiratory Function Tests , WalkingABSTRACT
<p><b>OBJECTIVE</b>To study the influence of several excipients on damp-proof performance of pharmaceutical materials of traditional Chinese medicine.</p><p><b>METHOD</b>The moisture absorption rate and parameters of hydroscopicity were used as the evaluation index of the damp-proof property of the complex Chinese medicine and preparation 1 and 2.</p><p><b>RESULT</b>The moisture rate of complex Chinese medicine 1 was 62.54%, the critical relative humidity (CRH) was 38%. The moisture rate of complex Chinese medicine 2 was 16.36%, the CRH was 53%. Excipients had different effect on lower the hyproscopic property of complex Chinese medicine 1 and 2. The initial moisture adsorption velocity of excipients of complex Chinese medicine 1 in a ascending order were dextrin < calcium hydrogen phosphate < micro crystalline cellulose < lactose < ethyl cellulose < mannitol < hydroxypropyl methyl cellulose. The moisture adsorption acceleration of excipients in a ascending order were dextrin = calcium hydrogen phosphate = micro crystalline cellulose < mannitol = ethyl cellulose = lactose < hydroxypropyl methyl cellulose. The moisture adsorption rate of excipients in a ascending order were dextrin < lactose < calcium hydrogen phosphate < ethyl cellulose < micro crystalline cellulose < mannitol < hydroxypropyl methyl cellulose. The initial moisture adsorption velocity of excipients of complex Chinese medicine 2 in a ascending order were mannitol < dextrin < calcium hydrogen phosphate < lactose < ethyl cellulose < micro crystalline cellulose < hydroxypropyl methyl cellulose . The moisture adsorption acceleration of excipients in a ascending order were mannitol = dextrin = calcium hydrogen phosphate < lactose < ethyl celluloselactose < micro crystalline cellulose < hydroxypropyl methyl cellulose. The moisture adsorption rate of excipients in a ascending order were mannitol < dextrin < calcium hydrogen phosphate < lactose < ethyl cellulose < micro crystalline cellulose < hydroxypropyl methyl cellulose.</p><p><b>CONCLUSION</b>The choosing of damp-proof excipients of preparation based on the property of the complex traditional Chinese medicine. The study provided experimental evidences for the research and development of the pharmaceutical materials of traditional Chinese medicine.</p>
Subject(s)
Absorption , Drugs, Chinese Herbal , Chemistry , Excipients , Chemistry , Humidity , Medicine, Chinese TraditionalABSTRACT
<p><b>OBJECTIVE</b>To prepare four breviscapine lipid carrier gels and general gel, and to study the transdermal promotive effects of them in vitro.</p><p><b>METHOD</b>Improved Franz-type diffusion cell and isolated rat skin were used as transdermal barrier, and the transdermal property was fitted by pharmacokinetics equations. The unit area cumulative permeation quantity of breviscapine was determined by HPLC method.</p><p><b>RESULT</b>The 24 hours' unit area cumulative permeation quantity of SLN gel was the highest, followed in descending order were transfersomal gel, liposomal gel, NLC gel and general gel. The transdermal property in vitro of SLN gel fitted in with Higuchi pharmacokinetics equation.</p><p><b>CONCLUSION</b>The lipid carrier gels had different transdermal promotive effects to breviscapine, SLN gel was the best one as breviscapine transdermal carrier.</p>
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Animals , Male , Mice , Administration, Cutaneous , Chemistry, Pharmaceutical , Methods , Drug Carriers , Chemistry , Drug Delivery Systems , Flavonoids , Chemistry , Pharmacokinetics , Lipids , Chemistry , Skin AbsorptionABSTRACT
<p><b>OBJECTIVE</b>To study Xionggui nasal sprays and its evaluation in release in vitro and absorption in vivo.</p><p><b>METHOD</b>Establishing the best prescription of Xionggui nasal sprays through orthogonal design methods, The in vitro release action of Xionggui nasal sprays was studied using dynamic dialyse method. The in vivo rat nasal recirculation methods were used to study the rule of Xionggui nasal sprays absorption.</p><p><b>RESULT</b>The optimum prescription was: Pemulen TR-1 0.35%, EDTA 0.2%, PEG400 1%, xanthan gum 0.2%; trolamine: right amount(adjust pH). Its release in vitro and absorption in vivo meet to Higuchi distribution.</p><p><b>CONCLUSION</b>The preparation method of Xionggui nasal sprays was appropriate. The release of drug and its uptake was well correlated.</p>
Subject(s)
Animals , Female , Male , Rats , Absorption , Administration, Intranasal , Aerosols , Angelica sinensis , Chemistry , Drug Carriers , Drug Combinations , Drug Compounding , Methods , Drugs, Chinese Herbal , Pharmacokinetics , Edetic Acid , Emulsions , Ethanolamines , Ligusticum , Chemistry , Nasal Mucosa , Metabolism , Plants, Medicinal , Chemistry , Polyethylene Glycols , Polysaccharides, Bacterial , Rats, Sprague-DawleyABSTRACT
From the characteristic, prepare the craft, quality control, bioavailability and clinical curative effect,etc. To do the summary to the modern research of dropping pill, analyse and is thought to dropping pill that has wide development prospects.
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Animals , Humans , Biological Availability , Capsules , Drugs, Chinese Herbal , Pharmacokinetics , Plants, Medicinal , Chemistry , Polyethylene Glycols , Quality Control , Solubility , Technology, Pharmaceutical , MethodsABSTRACT
<p><b>OBJECTIVE</b>To study the preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release.</p><p><b>METHOD</b>To prepare solid lipid nanoparticles (SLN) loaded with Xionggui powder-supercritical carbon dioxide fluid extraction (XG-CO2-SFE) using a hot dispersion- ultrasonic technique, establishing the best prescription of XG-CO2-SFE-SLN through orthogonal design methods using entrapment efficiency of nanoparticles as index, and investigating their physicochemical characterizations. The invro release action of SLN was studied in different dissolution mediums using dynamic dialyse method.</p><p><b>RESULT</b>The best prescription was: phospholipid: F-68: stearie acid glyceride = 5: 2 : 1, the entrapment efficiency of nanoparticles was 96.3%, and the results revealed the nanoparticles were sphere like with the mean size of 245.8 nm, the mean Zeta potential was -33.5 mV. The in vitro release meet to Weibull distribution in physiological brine and to single-index model in pH 7.4 phosphate liquid (40% EtOH).</p><p><b>CONCLUSION</b>The preparation method of the XG-CO2-SFE-SLN was appropriate, and the XG-CO2-SFE-SLN was released completely.</p>