Preparation modification strategies for clinical treatment drugs of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Research advances in the study of anticoagulant active molecules / 药学学报

The incidence of thrombosis-induced cardiovascular diseases is increasing worldwide and poses a serious threat to human health. Three factors, slow speed of blood flow, hypercoagulable blood and vascular damage, have been considered to be causes of thrombosis. Antithrombotic drugs have been classified into three categories based on the mechanism of thrombosis, including anticoagulants, platelet inhibitors and fibrinolytics. The coagulation and anticoagulation systems have drawn increasing attention because of the important role they play in the process of thrombosis. Novel compounds with anticoagulant activity are now emerging, alleviating to some extent some of the problems associated with the clinical use of early approved thrombotic drugs, such as high bleeding risk, slow onset of action and narrow therapeutic windows. In this review, we initially describe the mechanisms of coagulation as well as thrombosis. Meanwhile, a wide range of bioactive compounds and potential antithrombotic candidates reported in recent years have been summarized. In addition, the structure-activity relationship of certain compounds has been discussed, expecting to facilitate the development of molecules with anticoagulant biological activity for the treatment of thrombotic diseases.

Advances in taste masking technology based on preparation technology / 药学学报

Good medicine tastes bitter, but it is often difficult to swallow because the drug is bitter and astringent, so that the compliance of patients with medication is poor. However, the use of taste masking technology can better improve this situation. Appropriate and effective taste masking technology can improve the drug compliance of patients, especially children, it can also improve the curative effect and the clinical value of drugs. Herein, we summarize the latest research progress of taste masking technology, and summarize the traditional taste masking technology from the aspects of action mechanisms and application scopes. Finally, the novel and efficient taste masking technologies were presented.

Taste masking pharmaceutical excipients and their applications / 药学学报

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

Protective mechanism of Yinchenzhufu decoction against cholestatic liver injury induced by lithic acid based on network pharmacology / 药学学报

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI).@*METHODS@#Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively.@*RESULTS@#The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01).@*CONCLUSION@#CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.

Research progress of histidine-based tumor-targeting drug delivery systems / 药学学报

As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

Study on the cross-linking degree of PVPP by NMR technology and its powder compressibility / 药学学报

In this paper, the low-field nuclear magnetic resonance technology CPMG (Carr-Purcell-Meiboom-Gill) echo method was used to determine the cross-linking degree and cross-linking density of crospovidone (PVPP) from different manufacturers. Based on the seven physical properties of PVPP, a fingerprint spectrum (radar chart) of twenty secondary quality indicators were obtained, and three compressibility evaluation indicators, index of the parameter (IP), index of parametric profile (IPP), index of good compression (IGC) were calculated by the fingerprint spectrum. It was found that the cross-linking degree and compressibility index IP of PVPP showed a strong correlation (r = 0.816) by the correlation analysis, indicating that the cross-linking degree is one of the key quality attributes for evaluating the compressibility of PVPP.

An Integrated Digital Magnetic Resonance Imaging Spectrometer / 中国医疗器械杂志

An integrated digital magnetic resonance imaging spectrometer was proposed in this study. By using the FPGA chip Artix7 200T, timing control, data processing, digital frequency conversion and phase control were implemented into a single-chip, thus effectively improved timing accuracy and phase accuracy, while avoided the structural design complexity caused by multi-board connection and improved system integration and imaging quality.

Research progress on muscle spindle morphology / 生理学报

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

Treatment of spine metastases by open decompression, microwave ablation combined with open vertebroplasty and pedicle screw rod system / 中国骨伤

OBJECTIVE@#To evaluate the preliminary clinical effective of open decompression, microwave ablation combined with open vertebroplasty and pedicle screw rod system in the treatment of spine metastases.@*METHODS@#The clinical data of 12 patients with spine metastases were retrospectively analyzed, they were treated with open decompression, microwave ablation combined with open vertebroplasty and pedicle screw rod system between January 2014 and January 2016. Six males and 6 females were included, aged from 30 to 75 years old with an average of 55.6 years. There were 5 cases with spine metastases from lung cancer, 2 from breast cancer, 2 from thyroid cancer, 2 from renal cancer and 1 from liver cancer. Sevencases were thoracic metastases and 5 cases were lumbar metastases. Tomita score were mainly arranging from 3 to 6 points. According to ASIA neurologic grading system, 3 patients were grade C, 1 was grade D, 8 were grade E. Preoperative VAS score was 8.3±0.4. VAS was used to evaluate the clinical effect at 1, 3, 6 months after operation and final follow-up.@*RESULTS@#All operations were successful and the amount of blood loss during surgery was 500 to 2 050 ml (average of 850 ml), operation time was 3.5 to 5.5 h (average of 4.5 h). There was no nerve root injury during surgery. Cerebrospinal fluid leakage occurred in 3 cases after surgery, which were healed after conservative treatment. Superficial infection of the incision occurred in 2 cases, which were healed after dressing change. There was one case of pulmonary infection. No deep infection, lower limb thrombosis or other complications were found. All 12 patients were followed up for 9 -40 months with an average of 28.6 months. The clinical symptoms of all patients were significantly improved, and the motor function of the lower limbs was recovered to varying degrees. According to ASIA grade, 2 cases of grade C were improved to grade B;1 case of grade C did not recover significantly;1 case of grade D was improved to grade E. One patient died of primary liver cancer 10 months after surgery. Local tumor recurrence occurred in 1 patient during follow up period. The VAS scores were 2.7±0.6, 2.5±0.4, 2.6±0.5, and 2.5±0.5 at 1, 3, 6 months after surgery and at final follow-up, which were significantly improved compared with the score before surgery(<0.05).@*CONCLUSION@#Open decompression, microwave ablation combined with open vertebroplasty and pedicle screw rod system in the treatment of spine metastases show some effects, with less intraoperative blood loss, shorter operation time, significant postoperative pain relief, and low tumor recurrence rate.

Follistatin Like 5 (FSTL5) inhibits epithelial to mesenchymal transition in hepatocellular carcinoma / 中华医学杂志(英文版)

BACKGROUND@#Epithelial to mesenchymal transition (EMT) is a key process in determining distant metastasis and intra-hepatic dissemination of hepatocellular carcinoma (HCC). Follistatin (FST) family members are considered to be an attractive therapeutic targets and prognostic indicators in cancers. As a derivative of FST, Follistatin Like 5 (FSTL5) may play a similar role in HCC cells. This study aimed to investigate the expression and function of FSTL5 in HCC and its role in EMT.@*METHODS@#FSTL5, E-cadherin and vimentin in HCC, and paracancerous tissues were detected by immunohistochemistry. Correlation of FSTL5 expression with overall survival was assessed. The proliferation and invasion of HCC cell lines SK-Hep1 and MHCC-LM3 were analyzed by cell counting kit-8 and Transwell assays. The expression of FSTL5, E-cadherin, and vimentin in HCC cells was examined by polymerase chain reaction and Western blot analysis. T-test was used to analyze the difference in proliferation and invasion ability between groups. The Spearman rank correlation test was used to detect the correlation between the expression of FSTL5 and E-cadherin or vimentin.@*RESULTS@#The expression of FSTL5 in HCC was lower than that in paracancerous tissues (9.97% vs. 82.55%, χ = 340.15, P < 0.001). Patients with high FSTL5 expression had a better prognosis (χ = 8.22, P = 0.004) and smaller tumor diameter (χ = 45.52, P < 0.001), less lymph node metastasis (χ = 5.58, P = 0.02), earlier tumor node metastasis stage (χ = 11.29, P = 0.001), a reduced number of tumors (χ = 5.05, P = 0.02), lower alpha-fetoprotein value (χ = 24.36, P < 0.001), more probability of hepatitis carrying (χ = 40.9, P < 0.001), and better liver function grade (χ = 5.21, P = 0.02). Immunohistochemistry showed that FSTL5 expression in HCC tissues was positively correlated with E-cadherin expression (r = 0.38, P < 0.001) and negatively correlated with vimentin expression (r = -0.385, P < 0.001). Furthermore, over-expression of FSTL5 up-regulated the expression of E-cadherin and down-regulated the expression of vimentin in SK-Hep1 (negative control [NC] vs. FSTL5-interfering group [Lv-FSTL5]: E-cadherin [t = 45.03, P < 0.001], vimentin [t = 67, P < 0.001]) and MHCC-LM3 (NC vs. Lv-FSTL5: E-cadherin [t = 50, P < 0.001], vimentin [t = 72.75, P < 0.001]) cells at mRNA level. The same as protein level. In addition, the over-expression of FSTL5 inhibited the proliferation (NC vs. Lv-FSTL5: SK-Hep1, 3 d [t = 7.324, P = 0.018], 4 d [t = 6.23, P = 0.021], 5 d [t = 10.21, P = 0.003]; MHCC-LM3, 3 d [t = 4.32, P = 0.037], 4 d [t = 7.49, P = 0.012], 5 d [t = 9.3661, P = 0.009]) and invasion (NC vs. Lv-FSTL5: SK-Hep1, t = 21.57, P < 0.001; MHCC-LM3, t = 18.04, P < 0.001) of HCC cells.@*CONCLUSIONS@#Down-regulation of FSTL5 may contribute to EMT of HCC, and FSTL5 is a potential target in the treatment of HCC.

Determination of the K-value of different types of povidone by microfluidic rheometry and the relationship between K-value and weight-average molecular weight / 药学学报

italic>K-values of 56 batches of 7 types of povidone were measured by microfluidic rheometry and with a Ubbelohde capillary viscometer. The K-values of the two methods were tested by SPSS software and the results showed that there was no significant difference between the two methods (P > 0.05). Taking K-values measured with the Ubbelohde capillary viscometer (Ku) as the abscissa and K-values measured by microfluidic rheometry (Km) as the ordinate a linear equation was calculated: Km = 0.893 9Ku + 4.617 6, R2 = 0.986 2, with good linearity, indicating that the microfluidic rheometer method can replace the Ubbelohde capillary viscometer in determining K-values of povidone. The microfluidic rheometer method has the benefits of less sample consumption, faster determination, and is more accurate, and it can be used with high-throughput automatic acquisition, which provides a more convenient method for the determination of K-values of different types of povidone. The weight-average molecular weights (Mw) of each type of povidone were measured by gel permeation chromatography-multi angle laser light scattering (GPC-MALLS), and the relationship between Mw and Km was lgMw = -0.000 4 Km2 + 0.072 7 Km + 2.791, R2 = 0.990 1. The fitting relationship was good, and Mw could be calculated by Km by the equation.

Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma

Simultaneous inhibition of MDM2 and CDK4 may be an effective treatment against glioblastoma. A collection of chiral spirocyclic tetrahydronaphthalene (THN)-oxindole hybrids for this purpose have been developed. Appropriate stereochemistry in THN-fused spirooxindole compounds is key to their inhibitory activity: selectivity differed by over 40-fold between the least and most potent stereoisomers in time-resolved FRET and KINOMEscan® assays. Studies in glioblastoma cell lines showed that the most active compound induced apoptosis and cell cycle arrest by interfering with MDM2 -P53 interaction and CDK4 activation. Cells treated with showed up-regulation of proteins involved in P53 and cell cycle pathways. The compound showed good anti-tumor efficacy against glioblastoma xenografts in mice. These results suggested that rational design, asymmetric synthesis and biological evaluation of novel tetrahydronaphthalene fused spirooxindoles could generate promising MDM2-CDK4 dual inhibitors in glioblastoma therapy.

Evaluation of Residual Stepping Ability in Monkeys with Spinal Cord Injury / 中国康复理论与实践

Objective:To evaluate the residual stepping ability in monkeys with spinal cord injury longitudinally. Methods:Four adult female monkeys were studied. Right hemisection of 10 mm spinal cord tissue was performed at the T7-9 segment. Gait tests of bipedal locomotion were performed before, and six weeks and twelve weeks after injury by VICON system. Gait cycle duration, amplitude of knee and ankle angles, and ratio of united parameters were obtained from successive stepping and were quantitative analyzed. Results:The coordination of bilateral hindlimbs was destroyed after spinal cord injury, and the right hindlimb showed obviously dragging. The gait cycle duration of the left hindlimb increased significantly (P < 0.001), and the amplitudes of knee and ankle angle significantly increased (P < 0.001) after spinal cord injury. The ratio of united parameters was not statistically different among all the time points (P > 0.05). The gait cycle duration of the left hindlimb was correlated with step length (r = 0.838, P = 0.001), step height (r = 0.726, P = 0.007) and amplitude of ankle angle (r = 0.766, P = 0.004), and the amplitude of ankle angle was correlated with step length (r = 0.627, P = 0.029). Conclusion:The gait pattern of monkey with spinal cord injury has been changed. The gait strategy of the uninjured side was adjusted compensatively after spinal cord injury to adapt the functional impairment of contralateral hindlimb.

Clinical features analysis in 5 children of early onset epileptic encephalopathy with dyskinesia / 中国实用儿科杂志

OBJECTIVE: To investigate the clinical phenotype of children with early-onset epileptic encephalopathy and dyskinesia. METHODS: The patients with early onset epileptic encephalopathy and dyskinesia were enrolled from September 2013 to September 2017. The clinical data was retrospectively analyzed. RESULTS: A total of 5 children with early onset epileptic encephalopathy with dyskinesia were collected. Including 1 male and 4 females. 1 case of dyskinesia showed dancing-like movements,2 cases of dyslexia,ataxia mixed,1 case of limb tremor accompanied by wrist alternating twisting action,1 case of muscle tension associated with tremor,speech is unclear. 4 cases were positive for 1 genotype,1 case was mutation of SCN1A gene,2 cases were PRRT2 gene mutation,1 case was SLC2A1 gene mutation. After treatment,2 cases of seizure control effect is good,3 cases of poor results. CONCLUSION: Early onset epileptic encephalopathy with dyskinesia is easy misdiagnosed as epileptic seizures. Genetic associated with the pathogenic genes are mostly reported in the previous gene,PRRT2 gene,SLC2A1 gene mutation. Early onset of epilepsy with dyskinesia caused by SCN1A gene mutation has rarely been reported in the literature. Some children enjoy good results.

Relationship between retinopathy and urinary albumin/creatinine of hypertensive patients in a community of Suzhou / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the risk factors of retinal artery stenosis and its relationship with urinary albumin/creatinine in patients with hypertension, so as to provide a basis for prevention of target organ damage. <p>METHODS: In this study, a cross-sectional study was conducted in 1 983 patients with hypertension. According to the fundus examination, 944 patients were divided into normal group and 1 039 patients were divided into abnormal group. Baseline data were collected and urine albumin/creatinine was measured. Analysis of risk factors for retinal artery stenosis and its relationship with urinary albumin/creatinine.<p>RESULTS: There were significant differences in age and diabetes between the two groups(<i>P</i><0.05). Logistic regression showed that age(<i>OR</i>=1.013, <i>P</i>=0.011)and diabetes mellitus(<i>OR</i>=1.352, <i>P</i>=0.008)were risk factors for retinal artery stenosis. Hypertensive retinopathy(HR)detection rate was 95.56%. Grade I and grade II mild lesions were the major ones. The proportion of macroalbuminuria in retinal stenosis group was 65.59%, higher than that in microalbuminuria group(54.21%)and normal group(50.52%). <p>CONCLUSION: Age and diabetes are risk factors for retinal artery stenosis in hypertensive patients. Retinopathy is associated with urinary albumin/creatinine. The community should strengthen health education and early screening of retina and kidney to prevent the progress of the disease.

Optimization and characterization of deoxypodophyllotoxin loaded mPEG-PDLLA micelles by central composite design with response surface methodology / 中国天然药物

The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.

Preparation and in vitro evaluation of artemisinin loaded long-circulating liposomes / 药学学报

The therapeutic application of artemisinin (ART) is restricted in application due to its poor water solubility and stability. In this study, the long-circulating liposomes (L-Lip) were constructed to improve the solubility and stability of ART. The preparation method, physicochemical properties, serum stability, in vitro release profile and cytotoxicity of the ART loaded long-circulating liposomes were investigated. Using the particle size and entrapment efficiency (EE) as the evaluation index, the preparation procedure was optimized by the Box-Behnken response surface design based on the single factor screening method. The ART loaded long-circulating liposomes were prepared by filming rehydration method, and evaluated with particle size and entrapment efficiency. The optimal formulation was as follows:lipid-cholesterol=5.22:1 (mass ratio), drug-lipid=1:23.15 (mass ratio), lipid concentration=14.35 mg·mL-1, and molar percentage of mPEG=2%. The morphology of L-Lip was uniformly spherical shape according to optimal formulation. The mean size and polydispersity index (PDI) were about (113.3 ±4.7) nm and 0.227 ±0.022 respectively, the zeta potential was (-12.9 ±2.6) mV, and the entrapment efficiency (EE) of ART was (95.88 ±4.8)%. The L-Lip had good stability at 4℃ for 15 days and the particle sizes did not exhibit significant variations in 50% rat plasma over 24 h at 37℃. The in vitro release study of formulation showed a sustained release. Moreover, the cytotoxicity exhibited that blank liposomes were of great safety. Compared with the free ART, the liposome formulation achieved lower cytotoxicity at the high concentration. The L-Lip successfully prepared by a simple filming-rehydration method exhibited ideal physicochemical properties and were enhanced safety, which may sever as a promising nanoplatform for clinical application.

Optimization and characterization of deoxypodophyllotoxin loaded mPEG-PDLLA micelles by central composite design with response surface methodology / 中国天然药物

The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.