Recent advances of pharmaceutical 3D printing extrusion molding technology / 药学学报

3D printing is an additive manufacturing technology with the help of digital control. Since FDA approved the first 3D printing drug in 2015, its research enthusiasm in the pharmaceutical field has been increasing year by year. In printing technology, fused deposition molding (FDM) and semi-solid extrusion (SSE) are the two most widely used extrusion molding technologies. In this review, recent advances of pharmaceutical 3D printing extrusion molding technology are reviewed from six aspects: mechanism, equipment, pharmaceutical excipients, applications, design and industrialization prospects of extrusion molding technology.

Optimization and screening of carrier for solid dispersion of olaparib based on the solubility parameter and differential scanning calorimetry / 药学学报

Solid dispersion, a dispersion system in which drug molecules are highly dispersed in carrier materials, has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs. The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion. Therefore, the selection of carrier types and the optimization of drug loading are very important. In the current study, the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib (OLP) and different carriers (VA64, Soluplus, Plasdone S630 and Kollidon K29/32). Besides, the carrier material with good miscibility was experimentally screened by differential scanning calorimetry (DSC). The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier. Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best, and the drug loading of 30% could meet the requirements of large drug loading and physical stability. Polarizing light microscope, X-ray powder diffraction, DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system. Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP. In this study, theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading, which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.

Analysis of influencing factors on the prognosis of visual function in rhegmatogenous retinal detachment / 国际眼科杂志(Guoji Yanke Zazhi)

@#Rhegmatogenous retinal detachment(RRD)is the separation of the retinal nerve sensory layer and the pigment epithelium layer caused by retinal tears. It is a kind of ophthalmic emergency. If it is not treated in time, the blinding rate is close to 100%. Surgery is an important way to treat RRD. With the deepening of disease awareness and the improvement of retinal reattachment techniques, RRD reattachment has achieved a higher anatomical success rate, but in clinical, the postoperative visual experience of patients is still not ideal. This article mainly summarizes the influencing factors of RRD visual function prognosis and provides guidance for clinical treatment.

Mechanism of Scutellariae Radix-Hedyotidis Herba Against Proliferation of Lung Adenocarcinoma A549 Cells / 中国实验方剂学杂志

Objective:To observe the effects of Scutellariae Radix-Hedyotidis Herba on the proliferation of human lung adenocarcinoma A549 cells and the expression of interleukin-6（IL-6）， phosphatidylinositol 3-kinase （PI3K），protein kinase B （Akt）， p-protein kinase B （p-Akt）， mechanistic target of rapamycin （mTOR）， hypoxia-inducible factor-1<italic>α </italic>（HIF-1<italic>α</italic>）， and Cyclin D₁ at the cellular level， and to explore their molecular mechanism. Method:Following the set-up of the blank group （complete medium）， low-， moderate-，and high-dose （20， 40， and 60 mg·L^-1） Scutellariae Radix-Hedyotidis Herba groups， and low-， moderate-， and high-dose （5， 10， and 20 mg·L^-1） cisplatin groups， the cell were treated with the corresponding drugs for 24， 48， and 72 h for detecting their viability by tetrazolium bromide （MTT） colorimetry. A549 cells were then divided into the blank group， Scutellariae Radix-Hedyotidis Herba group， cisplatin group， and combined medication group and intervened with thecomplete medium， 40 mg·L^-1Scutellariae Radix-Hedyotidis Herba， 10 mg·L^-1 cisplatin， and 40 mg·L^-1Scutellariae Radix-Hedyotidis Herba + 10 mg·L^-1cisplatin， respectively， for 24， 48 and 72 h， followed by the measurement of inhibitory effects against the proliferation of A549 cells in each experimental group. The level of IL-6 in cell culture supernatant was determined by enzyme-linked immunosorbent assay （ELISA） after 72 h. The mRNA expression levels of HIF-1<italic>α</italic> and Cyclin D₁ in each group were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of PI3K， Akt， p-Akt， mTOR， HIF-1<italic>α</italic>， and Cyclin D₁ by Western blot. Result:After 24 h intervention， Scutellariae Radix-Hedyotidis Herba did not significantly inhibit the proliferation of A549 cells. However， 48 h later， the inhibitory effect in Scutellariae Radix-Hedyotidis Herba groups were significantly enhanced in comparison with that in the blank group （<italic>P</italic><0.05）， exhibiting a time-dependent response. After 72 h of action， no significant change was present in the inhibitory effect of each Scutellariae Radix-Hedyotidis Herba group， so the optimal concentration of Scutellariae Radix-Hedyotidis Herba was set at 40 mg·L^-1 for follow-up experiments. As demonstrated by the comparison with the blank group， cisplatin at each concentration inhibited the cell proliferation in a time-dependent manner （<italic>P<</italic>0.05）. Considering the cell survival rate， the best concentration of cisplatin was set at 10 mg·L^-1. Compared with the blank group， Scutellariae Radix-Hedyotidis Herba combined with cisplatin remarkably inhibited the proliferation of A549 cells in a time-dependent manner （<italic>P<</italic>0.05）， and the differences between the combined medication group and the other two groups became more significant after 72 h of medication （<italic>P<</italic>0.01）. The IL-6 level in each experimental group， especially in the combined medication group， significantly declined in contrast to that in the blank group （<italic>P<</italic>0.01）. The mRNA expression levels of HIF-1<italic>α</italic> and Cyclin D₁ in all experimental groups were obviously lower than those in the blank group， with the most significant changes observed in the combined medication group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The protein expression levels of PI3K， p-Akt， mTOR， HIF-1<italic>α</italic>， and Cyclin D₁ in each experimental group was significantly down-regulated（<italic>P</italic><0.05，<italic>P</italic><0.01）， and the levels in the combined medication group were even lower than those in the cisplatin group （<italic>P<</italic>0.01）. Conclusion:Scutellariae Radix-Hedyotidis Herba has an inhibitory effect on the proliferation of A549 cells， which may be related to its inhibition against the expression and secretion of IL-6/PI3K/Akt/mTOR-HIF-1<italic>α</italic> axis.

Effect of vitreomacular adhesion on anti-vascular endothelial growth factor therapy for branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the effect of vitreous macular adhesion(VMA)on the efficacy of anti-VEGF therapy in patients with branch retinal vein occlusion(BRVO).<p>METHODS: Retrospective case study. According to initially diagnosed OCT characteristics, 110 patients(110 eyes), selected from those who received intravitreal injection of Conbercept in the ophthalmology department of our hospital from January 2017 to May 2019,were divided into VMA-present group(VMA+ group, 34 eyes)and VMA-free group(VMA- group, 76 eyes). After the first injection, at least 6mo follow-up was ensured, to record the number of injection and to examine the best corrected visual acuity(BCVA)and central macular thickness(CMT). And it's <i>via</i> the OCT reports to evaluate status of the vitreous macular adhesion and the occurrence of posterior vitreous detachment(PVD).<p>RESULTS: During the 6mo follow-up after the first injection, there was no difference in the average number of intravitreal injections between patients in VMA+ group and VMA- group(2.91±1.05 times <i>vs</i> 3.08±1.22 times, <i>P</i>=0.915). At the 6mo after the first injection, BCVA and CMT were significantly improved in both groups, and BCVA gain in VMA+ group was more obvious than that in VMA- group \〖-0.20(-0.33, -0.10)LogMAR <i>vs</i> -0.20(-0.30, -0.10), <i>P</i>=0.041\〗, but there was no difference in CMT changes between the two groups(<i>P</i>=0.914). During this follow-up period, in the VMA+ group, 3 eyes, which were focal VMA at baseline, all developed into macular PVD(100.0%); and 5 of 31 eyes, which were extensive VMA at baseline, developed into macular PVD(16.1%). Compared with the extensive VMA, PVD was more likely to develop into focal VMA(<i>P</i>=0.009).<p>CONCLUSION: BRVO patients combined with VMA have greater potentiality in visual improvements under anti-VEGF treatments. Therefore, the presence of VMA does not prevent BRVO patients from receiving anti-VEGF therapy.