Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells / 中国中药杂志

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Efecto angiogénico comparado del celecoxib microencapsulado en PLGA v/s no encapsulado en un ensayo in vivo de angiogénesis / Comparative angiogenic effect of microencapsulated celecoxib in PLGA v/s non-encapsulated in an in vivo angiogenesis assay

RESUMEN: La angiogénesis es el proceso de formación de vasos sanguíneos a partir de otros formados previamente. Existen varios factores que están involucrados en el proceso, así como agentes capaces de modular distintas etapas de esta. Si bien, se ha observado que Celecoxib es capaz de inhibir la angiogénesis en distintos modelos, aún no se ha observado la potencial capacidad antiangiogénica de este agente cuando es microencapsulado en PLGA. Se incubaron huevos fertilizados y a las 48 horas se dividieron en 4 grupos para ser instilados con PBS (control), PLGA, Celecoxib 1000 ppm o Celecoxib 1000 ppm + PLGA. Se realizó un conteo de los vasos sanguíneos a las 48, 72 y 96 horas post aplicación de la solución a estudiar. Los resultados muestran que tanto Celecoxib como Celecoxib+PLGA reducen los vasos sanguíneos, manteniendo el mismo efecto a las 48, 72 y 96 horas y no existen diferencias significativas entre los dos tratamientos. Esto podría ser explicado por la concentración de Celecoxib usada o el margen de tiempo analizado, pudiendo encontrarse diferencias posteriores a este rango de tiempo o con concentraciones distintas.

SUMMARY: Angiogenesis is the process of blood vessel formation from previously formed ones. There are several factors involved in the process, as well as agents capable of modulating different stages of it. Although, it has been observed that Celecoxib is capable of inhibiting angiogenesis in different models, the potential antiangiogenic capacity of this agent has not yet been observed when it is microencapsulated in PLGA. Fertilized eggs were incubated and at 48 hours they were divided into 4 groups to be instilled with PBS (control), PLGA, Celecoxib 1000ppm or Celecoxib 1000 ppm + PLGA. A blood vessel count was performed at 48, 72 and 96 hours after application of the solution to be studied. The results show that both Celecoxib and Celecoxib + PLGA reduce blood vessels, maintaining the same effect at 48, 72 and 96 hours and there are no significant differences between the two treatments. This could be explained by the concentration of Celecoxib used or the time frame analyzed, being able to find differences after this time range or with different concentrations.

Development and characterization of PLGA-Bupivacaine and PLGA-S75: R25 Bupivacaine (Novabupi®) biodegradable implants for postoperative pain

Abstract In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.

Management of recurrent polymorphous low grade adenocarcinoma: a case report / Manejo de adenocarcinoma polimorfo recorrente de baixo grau: relato de caso

The Polymorphous Low Grade Adenocarcinoma (PLGA) is a common minor salivary gland carcinoma. It mostly affects the buccal mucosa and retromolar region, but the palate is an unusual site. As the carcinoma is low grade the recurrence is also uncommon. Our patient had a PLGA initially in the palate which was treated initially through surgical management but had a recurrence after four years. Hence we planned a partial maxillectomy along with level I nodes. Post-operatively follow-up is successful till date. So the management of a recurrent PLGA through careful surgery and post-operative follow ­up with prosthetic rehabilitation is discussed in this article... (AU)

Construction and in vivo evaluation of a thermosensitive hydrogel system loading with Pseudomonas aeruginosa DNA vaccine / 中国药科大学学报

@#A thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine was constructed and the immune efficacy of the system was evaluated. The PLGA-PEG-PLGA thermosensitive hydrogel containing Pseudomonas aeruginosa DNA vaccine was prepared by a simple physical mixing method. The gelation temperature, cytotoxicity, and release curve in vitro were tested.The degradability of hydrogel in vivo was evaluated. The mice were divided into control group (PBS), hydrogel group (Hydrogel), in vivo-jetPEI/plasmid DNA group (in vivo-jetPEI/pDNA), and hydrogel + in vivo-jetPEI/plasmid group (Gel+in vivo-jetPEI/pDNA). Mice were immunized three times with a ten-day interval. Two weeks after the last immunization, the mice were sacrificed. The proliferation of splenic lymphocytes, serum specific IgG antibodies and IFN-γ in supernatant of splenic lymphocytes were detected. The gelation temperature of PLGA-PEG-PLGA hydrogel was (32 ± 0.5) ℃. There was no obvious toxicity to cells in vitro, and about 80% of plasmid DNA was released after 7 days in vitro. PLGA-PEG-PLGA hydrogel was biodegradable, and degraded almost completely after 15 days in vivo. The spleen lymphocytes proliferated; the levels of specific IgG antibodies and IFN-γ of in vivo-jetPEI/pDNA and Gel+in vivo-jetPEI/pDNA groups increased. The hydrogel could enhance the immune response induced by DNA vaccine.Results suggest that the thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine is a promising new strategy for the development of PA vaccine.

Formulation Optimization and Characterization of Docetaxel PELGE Nanoparticles and Preliminarily Evaluation of Its Drug Release and Antitumor Activity in vitro / 中国药房

OBJECTIVE：To optimize the f ormulation of docetaxel （DTX）-mPEG-PLGA-mPEG （PELGE）-nanoparticles （NPs），and to characterize it and evaluate its in vitro drug release and antitumor activity. METHODS ：PELGE were synthesized by ring-opening polymerization. DTX-PELGE-NPs were prepared by using emulsion solvent evaporation method. The content of DTX in DTX-PELGE-NPs was determined by HPLC. Box-Behnken design-response surface methodology was applied to optimize the formulation of the nanoparticles using the amount of DTX ，PELGE and poloxamer 188 as independent variable ，using entrapped efficiency as dependent variable. The particle size and Zeta-potential of DTX-PELGE-NPs were characterized by laser particle size analyzer and transmission electron microscope. The in vitro release of the DTX-PELGE-NPs was investigated by ultra-filtered centrifugation，using DTX injection as reference. In vitro cytotoxicity of the DTX-PELGE-NPs was investigated by MTT assay ， using DTX and PELGE-NPs without DTX as reference . RESULTS ：The optimal formulation included 2.80 mg DTX ，20.60 mg PELGE and 6％ poloxamer 188. The entrapped efficiency of optimized DTX-PELGE-NPs was （86.79±1.32）％；drug-loading amount was （10.21±0.78）％，and average particle size was （78.4±2.9）nm；polydispersity coeffici ent was （0.187±0.018）and Zeta potential was （－20.6±1.5）mV. Furthermore ，DTX- PELGE-NPs showed a regular spherical and uniform distribution under scanning electron microscopy. Compared with DTXinjection（accumulative release rate of 92.3％ at 4 h），DTX- PELGE-NPs had a significant sustained-release effect （accumu-lative release rate of 78.6％ at 36 h）. 0.1-50 μg/mL PELGE-NPs had no obvious cytotoxicity to human breast cancer cells MCF-7（P＞0.05）. 0.5-10 μg/mL DTX-PELGE-NPs could significantly inhibit the growth of human breast cancer cells MCF-7， and its inhibitory effect （except for DTX-PELGE-NPs 10 μg/mL group）was significantly stronger than that of DTX injection （P＜ 0.05）. CONCLUSIONS ：The optimized formulation is stable and feasible. The obtained DTX-PELGE-NPs not only have uniform particle size ，high encapsulation rate obvious slow-release effect ，but also have stronger anti-tumor effect in vitro than DTX injection.

Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles / 中国药科大学学报

@#To construct PTEN/PLGA-(HE)10-MAP nanoparticles, which encapsulated PTEN plasmid DNA and combined with the pH-responsive cell-penetrating peptides (CPPs), and to investigate their effects of gene delivery and anti-tumor targets in vitro. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTEN plasmid DNA were prepared by double emulsification-solvent evaporation method. PTEN/PLGA-(HE)10-MAP nanoparticles were prepared by coupling the histidine-glutamic acid-model amphipathic peptide nanocomplex [(HE)10-MAP] to the surface through amide condensation reaction. Particle size, Zeta potential, encapsulation rate and drug loading were tested to characterize the nanoparticles. By analyzing the cytotoxicity, cellular uptake, targeted transfection of eukaryotic expression plasmids and anti-tumor cell proliferation, the feasibility as a targeted gene delivery system were evaluated. The particle size of PTEN/PLGA-(HE)10-MAP nanoparticles was (266.5 ± 2.86) nm, with the encapsulation efficiency (80.6 ± 6.11)%. Zeta potentials were -(6.7 ± 0.26) mV, +(0.7 ± 0.22) mV and +(37.5 ± 0.85) mV at pH 7.4, 7.0 and 6.5, respectively. In the cytotoxicity test, the cell survival rates of tumor and normal cells were above 80%.Non-loading PLGA-(HE)10-MAP nanoparticles showed no obvious cytotoxicity. The results of cellular uptake experiments showed that PTEN/PLGA-(HE)10-MAP nanoparticles were more readily taken up by cells.The results of CCK-8 showed that the nanoparticles could pH-specifically inhibit proliferation of tumor cell in vitro.And PTEN/PLGA-(HE)10-MAP nanoparticles may be applied in tumor gene therapy.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).

Preparation of paclitaxel-loaded and folic acid-modified poly (lactic-co-glycolic acid) nano-micelles and in vitro anticancer effect on cervical cancer HeLa cells / 中国中药杂志

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.

Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles

Background: Cisplatin is a widely-used potent anti-cancer drug having severe side-effects precluding itssustained use.Objectives: Poly (lactide-co-glycolide) (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient ofethanolic extract of Boldo plant (Peumus boldus) was tested in cancer mice model, Mus musculus toexamine if it could reduce unwanted Cisplatin-induced toxicity in normal tissue.Material and methods: Nano-encapsulation of Boldine was done by following the standardized solventdisplacement method. Physico-chemical characterization of PLGA-encapsulated nano-Boldine (NBol) wasaccomplished through analyses of various spectroscopic techniques. Status of major antioxidant enzymes, functional markers, and lipid peroxidation (LPO) was also determined in certain tissue and serumsamples. Percentage of cells undergoing cytotoxic death, Reactive oxygen species (ROS) accumulationand mitochondrial functioning were analyzed in both normal and cancer mice. Nanoscale changes inchromatin organization were assessed by Transmission electron microscopy (TEM). mRNA and proteinexpressions of Top II, Bax, Bcl-2, Cyt c, caspase 3 were studied by RT-PCR, immunoblot andimmunofluorescence.Results: NBol had faster mobility, site-specific action and ability of sustained particle release. NBol readilyentered cells, prevented Cisplatin to intercalate with dsDNA resulting in reduction of chromatincondensation, with corresponding changes in ROS levels, mitochondrial functioning and antioxidantenzyme activities, leading to reduction in Deoxyribose nucleic acid (DNA) damage and cytotoxic celldeath. Expression pattern of apoptotic genes like Top II, p53, Bax, Bcl-2, cytochrome c and caspase-3suggested greater cytoprotective potentials of NBol in normal tissues.Conclusions: Compared to Boldine (Bol), NBol had better ability of drug carriage and protective potentials(29.00% approximately) against Cisplatin-induced toxicity. Combinational therapeutic use of PLGA-NBolcan reduce unwanted Cisplatin-induced cellular toxicity facilitating use of Cisplatin.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Construction of periodontal biomimetic membrane with electrospun poly(Lactic-co-glycolic acid) nanofibers and electrosprayed chitosan microspheres / 中国组织工程研究

BACKGROUND: When the teeth are separated from the alveolar fossa, the periodontal membrane breaks, and the residual periodontal membrane on the avulsed tooth root surface changes from three-dimensional to two-dimensional, thus losing the role of scaffold, and leading to root bone adhesion after replantation of avulsed tooth. How to develop a three-dimensional sustained-release scaffold material that can adhere to the root surface with a certain thickness and strength is one of the key factors for successful regeneration of avulsed tooth periodontal membrane. OBJECTIVE: To construct a three-dimensional periodontal biomimetic membrane that can adhere to the avulsed tooth root surface and allow sustained-release of growth factors. METHODS: Poly(lactic-co-glycolic acid) (PLGA) membrane was prepared using electrospinning technique. The effects of dichloromethane and dimethylformamide mixture, hexafluoroisopropanol, and trichloromethane on electrospun membrane were investigated to obtain the optimal electrospinning solvent. Chitosan microspheres were prepared by electrospray and ion cross-linking techniques. The effects of molecular weight (50, 000, 100, 000) and mass concentration (10, 20 g/L) of chitosan, sodium tripolyphosphate concentration (2%, 5%, 10%) and voltage (14, 28 kV) on chitosan microspheres were studied to screen the optimum parameters. Chitosan microspheres containing stromal cell-derived factor-1 (optimal parameter design) were constructed. The release rate of stromal cell-derived factor-1 alpha in vitro was determined. First, the root surface of teeth was wrapped with electrospun PLGA membrane, then chitosan microspheres were dripped on the surface, and finally the surface was wrapped with a thin layer of electrospun PLGA. Thus, PLGA-chitosan-PLGA biomimetic membrane was constructed. RESULTS AND CONCLUSION: Electrospun PLGA membrane prepared with hexafluoroisopropanol as electrospinning solvent had the smallest average diameter and the largest porosity. When the relative molecular weight of chitosan was 50, 000 and the mass concentration was 20 g/L, the size of chitosan microspheres was basically the same, and the average diameter was 366. 6 μm. In addition, chitosan microsphere had good monodispersity, fullness, and stability. Chitosan microspheres formed under 28 kV voltage and were more in line with the requirements of biomimetic membrane for avulsed tooth. The surface of microspheres prepared by 5% sodium tripolyphosphate had medium-sized pores, which are most conducive to clinical periodontal membrane regeneration. Chitosan microspheres can sustainably release stromal cell derived factor 1alpha for about 1 month. In this study, we constructed a three-dimensional PLGA-chitosan-PLGA periodontal biomimetic membrane that can adhere to the avulsed tooth root surface and allow sustained-release of growth factors and obtained the optimal parameters of constructing the periodontal biomimetic membrane. Based on the PLGA-chitosan-PLGA periodontal biomimetic membrane, the effect and mechanism of tissue engineering on replantation of avulsed tooth can be further studied.

PLGA- corosolic acid implants for potential application in ocular neovascularization diseases

Angiogenesis is the formation of new blood vessels from preexisting vasculature. Uncontrolled angiogenesis is associated with progression of several ocular pathologies, such as diabetic retinopathy and macular degeneration. Thus, the inhibition of this process consists in an interesting therapeutic target. Corosolic acid (CA) is a natural derivative of ursolic acid, found in many medicinal herbs and exhibits numerous biological properties, including the antiangiogenic activity. The present study reports the production of CA-loaded poly d,l-lactidecoglycolide acid (PLGA) devices by melt technique. HPLC-UV method was developed and validated to evaluate the uniformity and the release profile of the developed systems. The devices were also characterized by Fourier transform infrared spectroscopy, thermal analysis, and scanning electron morphology. It was studied the antiangiogenic activity of the CA-polymer system, using an in vivo model, the chorioallantoic membrane assay (CAM). CA was dispersed uniformly in the polymer matrix and no chemical interaction between the components of the formulation was verified. The implants presented a sustained release of the drug, which was confirmed by the morphological study and demonstrated an antiangiogenic activity. Therefore, the developed delivery system is a promising therapeutic tool for the treatment of ocular diseases associated with neovascularization or others related to the angiogenic process.

Tadalafil-loaded PLGA microspheres for pulmonary administration: preparation and evaluation

Tadalafil, a long-acting PED-5 inhibitor, is commonly used for the treatment of pulmonary arterial hypertension (PAH). However, its efficacy and clinical application are severely limited by the poor water solubility, low bioavailability and a series adverse effects (e.g. headaches, indigestion). In this study, tadalafil was prepared and loaded into biodegradable PLGA (poly(lactic-co-glycolic acid)) microspheres (TDF-PLGA-MS) via emulsification-solvent evaporation. The resulting microspheres were processed into pulmonary inhalant by freeze drying. The TDF-PLGA-MS was spherical and uniform, with an average particle diameter ~10.29 µm. The encapsulation efficiency and drug loading yield of TDF-PLGA-MS were 81.68% and 8.52%, respectively. The investigation of micromeritics showed that the TDF-PLGA-MS had low moisture content. The fluidity of powders was relatively good. The aerodynamic diameter and emptying rate of microspheres powders were 3.92 µm and 95.41%, respectively. Therefore, the microspheres powders were easy to be atomized, and can meet the requirements of pulmonary administration. In vitro release results showed that the microspheres group released slowly. The cumulative release in 24 h and 10 d was 46.87% and 84.06%, respectively. The in vitro release profile of TDF-PLGA-MS was in accordance with the Weibull model. The results of Pharmacokinetics showed that tadalafil from microspheres slowly released into the blood after intratracheal instillation. The pulmonary drug residue in 0.5 h was 3.5 times compared with solution group. The residual concentration in lung after 10d was still higher than that of solution group in 48 h. The t1/2β and MRT0-∞ were 3.10 times and 3.96 times that of solution group, respectively. Moreover, the Cmax and AUC of drug residues in lung ​​were 3.48 times and 16.36 times that of solution group, respectively. The results of tissue distribution showed that the Re in lung was 16.358, which indicated the lung targeting. In conclusion, the TDF-PLGA-MS for pulmonary administration in this study can significantly improve the pulmonary targeting, increase efficacy of tadalafil and reduce other non-target organs toxicity. This study will have an important clinical significance for PAH patients who need long-term drug therapy.

Preparation of Juglone-loaded PLGA Nanoparticles and Its Anti-tumor Effect on Melanoma A375 Cells in Vitro / 中国实验方剂学杂志

Objective: To prepare Juglone-loaded poly lactic-co-glycolic acid nanoparticles (Jug-PLGA-NPs), and investigate their physicochemical properties, release characteristics in vitro and anti-tumor activities on A375 melanoma cells in vitro. Method: Jug-PLGA-NPs were prepared by emulsification-solvent evaporation method. Then the particle size, encapsulation efficiency, drug loading rate and in vitro release characteristics were investigated. Fluorescence microscopy was used to observe the uptake of PLGA-NPs in vitro. The distribution of PLGA-NPs in BALB/c nude mice after tail vein injection was observed by the small living animal imaging system. Their inhibition effect on proliferation of A375 cells was detected by thiazolyl blue tetrazolium bromide (MTT) assay. Apoptosis rate and cell cycle detection were performed by flow cytometry. Western blot was used to determine the protein kinase B (Akt), phosphorylated Akt (p-Akt) and cyclinD1. Result: The average particle size of the prepared Jug-PLGA-NPs was (149.6±21.5) nm, entrapment rate of (68.39±2.51)%, and drug-loading rate of (5.07±0.98)%, showing good sustained-release characteristics. PLGA-NPs showed good penetration and targeting properties in cellular uptake in vitro and in vivo imaging. Different concentrations of Jug-PLGA-NPs could significantly inhibit the proliferation and promote apoptosis of A375 cells in a time and concentration dependent manner (P1 expression (P0/G1 phase (PConclusion: The Jug-PLGA-NPs are easy to prepare and have good sustained-release characteristics, tumor targeting and anti-tumor ability, providing a new pharmaceutical dosage form for the future clinical application of Jug.

Progress in the Industrialization of Sustained-release Microsphere / 中国药学杂志

Recently, drug-loading microspheres prepared from biodegradable polymers have attracted great attentions. It is a hot topic in the research of pharmaceutical preparations because it can be used to control release of the drug. The selection of suitable polymer materials and production technology are the key factors for preparing sustained release microspheres. With the launching of many control release microspheres, the technology has been developed into a mature technology, and it has been shown to be controllable and industrialized. This paper mainly introduces the industrialized production technology of microspheres and some new technologies for preparing microspheres, as well as the drugs that have been marketed.

Study on preparation of curcumin-PLGA nanoparticles and their effect on apoptosis in glioma cells / 中国药理学通报

Aim To prepare curcumin-PLGA nanoparticles [curcumin poly(lactic-co-glycolic acid) nanoparticles, Cur-PLGA-NPs ] and evaluate their effects on glioma cells in vitro. Methods C6 cells and U251 cells were subcultured and randomly divided into control group, curcumin group and curcumin-PLGA group. The morphology of Cur-PLGA-NPs was observed by inverted fluorescence microscope and transmission electron microscopy. The particle size of Cur-PLGA-NPs was detected by Malvem particle size potentiometer. The encapsulation efficiency and drug loading rate of Cur-PLGA-NPs were detected by a multi-function microplate reader. The uptake of Cur-PLGA-NPs by C6 cells and U251 cells was observed by fluorescence microscopy. The effect of Cur-PLGA-NPs on the viability of C6 cells and U251 cells was detected by CCK-8. The effect of Cur-PLGA-NPs on apoptosis was assessed by flow cytometry. Apoptosis was detected by Hoechst staining. Results The Cur-PLGA-NPs had an average particle size of (284. 6 ± 9. 0) nm and were spherical. The encapsulation efficiency was (70.712 ±2.615)%, and the drug loading rate was (2.828 ±0.105) %. Compared with control group and curcumin group, C6 cells and U251 cells significantly increased the uptake of Cur-PLGA-NPs (P < 0. 05). Compared with control group and curcumin group, the cell viability of C6 cells and U251 cells in curcumin-PLGA group significantly decreased (P < 0. 05). Compared with control group and curcumin group, the Cur-PLGA-NPs induced apoptosis significantly in C6 cells and U251 cells(P <0. 05). Conclusion Compared with curcumin, Cur-PLGA-NPs can enhance the uptake of drugs by tumor cells, promoting tumor cell apoptosis.

Preparation and characterization of ginkgolide K-loaded PLGA-PEG nanoparticles and its neuroprotective activity in vitro / 中草药

Objective To prepare and characterize ginkgolide K-loaded mPEG-PLGA [poly (D,L-lactide-co-gly-colide)-block-poly (ethylene glycol)] polymer nanoparticles (GK-mPEG-PLGA-NPs) and to evaluate its neuroprotective effect on the H2O2-induced PC12 cells injury in vitro. Methods The PLGA-PEG-COOH polymer was selected as carrier and double emulsion solvent evaporation technique was employed to prepare the stealth nanoparticles. The encapsulation efficiency (EE) and drug load (DL) of GK-mPEG-PLGA-NPs were investigated by HPLC. The size distribution, zeta potential, and surface morphology of GK-mPEG-PLGA-NPs were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The in vitro release of GK-mPEG-PLGA-NPs was examined using phosphate buffer solution (pH 7.4) as the releasing medium for 24 h. The H2O2-induced PC12 cells injury models was established for the investigation of the protective effect of GK-mPEG-PLGA-NPs on nerve cells in vitro. Results EE and DL of GK-mPEG-PLGA-NPs was (83.40 ± 2.85)% and (3.26 ± 0.24) mg/g, respectively. The average diameter of GK-mPEG-PLGA-NPs was (93.19 ± 2.77) nm and zeta potential was (-11.93 ± 1.71) mV. The cumulative rate of drug release was (90.5 ± 4.0)% after 60 h in phosphate buffer solution. GK-mPEG-PLGA-NPs significantly inhibited the apoptosis of PC12 cells and the release of lactic dehydrogenase induced by H2O2. However, the protective action of GK-mPEG-PLGA-NPs on the H2O2-iduced PC12 cells injury was significantly weaker than that of GK. Conclusion Our results proved that GK-mPEG-PLGA-NPs had a sustained release behavior in vitro and the neuroprotective effect of GK-mPEG-PLGA-NPs on H2O2-induced PC12 cells, which indicates that GK-mPEG-PLGA-NPs has the prospect of application and deserves further research. Key words: ginkgolide K; mPEG-PLGA; in vitro release; in vitro neuroprotection; d

Optimazation of preparation of syringopicrosides PLGA nanopartides by central composite design-response surface methodology / 中草药

Objective: To optimize the formulation of syringopicrosides poly (lactic-co-glycolic acid, PLGA) nanoparticles (Syr-NPs). Methods: Syr-NPs were prepared by nanoprecipitation method. The encapsulation efficiency (EE), drug loading (DL), average particle size and general evaluation "normalized value" were used as evaluation indexes. The central composite design was used to inspect the effects of the concentration of PLGA (A), the concentration of syringopicrosides (B), the ratio of aqueous phase to organic phase (C) on three evaluation indexes mentioned above and the "normalized value" ofgeneral evaluation. Prediction and analysis for selecting the best prescription condition were carried out by using the central composite design-response surface method. Results: The concentration of PLGA, the concentration of syringopicrosides and the ratio of aqueous phase to organic phase according to the optimized prescription were 9.63 mg/mL, 12.88 mg/mL and 1:9.46, respectively; And the EE, drug loading and average particle diameter of Syr-NPs prepared according to the optimized prescription were (27.86 ± 0.87)%, (7.02 ± 0.15)%, and (110.0 ± 1.20) nm, respectively. Conclusion: This method is stable and feasible and can be used to optimize the formulation and preparation process of syringopicrosides wrapped inside with PLGA nanoparticles.

In vitro study of GOD/Fe3O4 loaded PLGA nanoparticles in the treatment of retinoblastoma / 解放军医学杂志

Objective To evaluate the therapeutic potential of a novel type of Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with glucose oxidase (GOD)/superparamagnetic iron oxide nanoparticles (Fe3O4Nps) on retinoblastoma (RB) cells in vitro. Methods PLGA nanoparticles loaded with GOD/Fe3O4 (PFG) were prepared by double emulsification. Their particle size, potential, external morphology, and internal structure were examined. Particles that made of PLGA (control), PLGA loaded with GOD (PG), and PLGA loaded with Fe3O4 (PF) are served as control. Y79 cells that were incubated with different particles are termed control group, PF group, PG group, and PFG group. After co-incubation with nanoparticles, cell viability, and reactive oxygen species production were detected. Results PLGA nanoparticles loaded with GOD/Fe3O4 were successfully prepared. The form of PLGA nanoparticles was uniform and showed a round shape with a diameter of 299.3 nm. The nanoparticles were engulfed by Y79 cells after co-incubation with Y79 cells, producing a large number of reactive oxygen species. Cytotoxicity test results showed that the cell viability of Y79 cells in PLGA nanoparticle group coated with GOD/Fe3O4 [(53.648±2.565)%] was significantly lower than that in control group [(100.028±4.491)%], PF group [(97.782±17.520)%] or PG group [(87.438±3.537)%](F=21.226, P<0.01); The cell viability of Y79 cells in 0.25 μg/ml PFG nanoparticle group [(51.770±1.529)%] was significantly lower than that in control group [(100.000±5.021)%], 0.0625 μg/ml group [(85.723±6.903)%] and 0.125 μg/ml group [(74.535±8.282)%] (F=34.593, P<0.05). Massive cell death was detected in the PFG group under laser confocal microscope. Conclusions The novel type of PLGA nanoparticles loaded with GOD/Fe3O4 toxic to Y79 tumor cells with a good reactive oxygen generation ability. It provides a potential treatment for RB.