To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.
Administration, Inhalation ; Drug Carriers ; chemistry ; Dry Powder Inhalers ; Lactose ; chemistry ; Particle Size ; Peptides ; administration & dosage ; Powders ; administration & dosage ; Surface Properties ; Technology, Pharmaceutical

Objective To investigate the relationship between autophagy and metastasis of nasopharyngeal cancer ( NPC) cell lines 5?8F and 6?10B after X?ray irradiation and the related mechanism. Methods Two substrains, 5?8F and 6?10B, of the NPC cell line SUNE1, with high and low metastatic potentials, respectively, were used in our study. After 4 Gy X?ray irradiation, 5?8F cells were treated with rapamycin ( 20 μmol/L) to induce autophagy and 6?10B cells were treated with LY294002( 10μmol/L) to inhibit autophagy. The autophagy and metastatic activity of NPC cells were determined using qRT?PCR, Western blot, Transwell assay, laser confocal microscopy, and transmission electron microscopy. Results 5?8F cells showed a lower level of autophagy than 6?10B cells after X?ray irradiation. Rapamycin increased the autophagy and inhibited the metastasis of 5?8F cells after irradiation, while LY294002 inhibited the autophagy and increased the metastasis of 6?10B cells. Conclusions NPC 5?8F cells, which have a high metastatic potential, have a lower level of autophagy than 6?10B cells, which have a low metastatic potential. Autophagic inhibition could increase the metastatic activity of NPC cells, while autophagic activation could reduce their metastatic activity. Mechanistic analysis indicates that the PI3K/AKT/mTOR pathway is involved in this process.

Using high pressure homogenization method combined with spray-drying, budesonide-loaded chitosan microparticles were prepared and the in vitro release profile was investigated. The microparticles were then blended with lactose using a vortex mixer, influence of mixing speed, mixing time on drug recovery rate and content homogeneity were investigated. Meanwhile, influence of lactose content on drug recovery rate, content homogeneity, powder flowability and in vitro deposition were studied. It turned out that budesonide was released from the microparicles in a sustained manner, with fine particle fraction as high as 46.0%, but the powder flowability was poor. After blending with 10 times of lactose, the drug recovery rate was 96.5%, with relative standard deviation of drug content 2.5%, and fine particle fraction of the formulation increased to 59.6% with good flowability. It's demonstrated that using a vortex mixer, budesonide sustained-release dry powder for inhalation with good recovery and content homogeneity could be prepared, the formulation had good flowability and was suitable for pulmonary inhaling.
Administration, Inhalation ; Budesonide ; chemistry ; Chemistry, Pharmaceutical ; Chitosan ; Delayed-Action Preparations ; chemistry ; Drug Carriers ; Lactose ; chemistry ; Particle Size ; Powders

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
Drug Carriers ; chemistry ; Fluorescence ; Kinetics ; Micelles ; Particle Size ; Poloxamer ; chemistry ; Solubility ; Stilbenes ; chemistry ; Water

Objective To compare the feasibility and safety of endoscopy with laparoscopy and without for gastric stromal tumor.Methods A retrospective and comprehensive analysis was made based on the clinical data of endoscopic (53 cases) and laparoscopic (39 cases) resection for gastric stromal tumor (diameter ＜ 3 cm with clear boundary),by comparing the operation time,intraoperative blood loss,indwelling time of postoperative gastric tube,recovery time of bowel functions,postoperative complications,hospitalization time,metastasis,recurrence rate.Results Compared with the laparoscopic group,the endoscopic group required shorter operation time [50(48-58) min VS 70 (50-95) min,U =1575.00,P ＜ 0.01],less intraoperative blood loss [10 (5-15) ml VS 20 (20-30) ml,U =1794.00,P ＜ 0.01],earlier recovery of bowel functions [18 (8-36) h VS 24 (20-40) h,U =1666.00,P ＜ 0.01],hospitalization time,indwelling time of the postoperative gastric tube and postoperative complications showed no statistical difference (P ＞ 0.05).The postoperative follow-up time were (27 + 15) and (24 + 11) months in the endoscopic and laparoscopic group,respectively (t =0.3084,P ＞ 0.05).During the follow-up,no tumor recurrence or distant metastasis was discovered,nor was death of gastric stromal tumor.Conclusion Endoscopy without the assist of laparoscopy for the gastric stromal tumor,whose diameter is less than 3 cm with clear boundary,is safe and less invasive,and leads to quick recovery.

Objective Islet transplantation has been an effective method for diabetes mellitus. The quality of donor pancreas is important for successful islet isolation. In this study, we evaluated expanded criteria donor usability based on the warm ischemic time, fatty pancreas and perfusion injury. Methods The marginal pancreases include those from cardiac death donor, fatty pancreas and edema pancreas from perfusion injury. Islets were isolated and purified using a modified University of Minnesota method. Islet yield and purity was determined by Dithizone (DTZ) staining and microscopic examination. Islet viability was assessed by AO/EB staining, and islet function was assessed by static glucose stimulation test. Results In the cardiac death donor group, the islet quality, viability, and in vitro function were similar when the warm ischemic time within 15 min. The quality and viability was decreased when the warm ischemic time beyond 30 min, but the function remained well. With 45 min warm ischemic time, insulin release index was decreased significantly. The islet quality, viability, and in vitro function from severe obesity group and severe edema group were decreased obviously. Conclusion Donor factors play a vital role in pancreas transplant outcomes. We concluded that pancreas severe obesity, severe edema and pancreas from cardiac donors (warm ischemic time ＞30 min) are unsuitable for islet isolation.

Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.

AIMTo prepare solid lipid nanoparticles by microemulsion technique.

METHODSStearic acid was used as the oil phase, lecithin as surfactant, alcohol as cosurfactant and distilled water as the aqueous phase. Microemulsion was prepared by mixing the above component in proper ratio. The corresponding pseudoternary phase diagram monitored Microemulsion formation field of different lecithin/alcohol. Solid lipid nanoparticles (SLN) were prepared by dispersing warm microemulsion in cold water under magnetic stirring. Then appropriate microemulsions that can contain more water phase and suitable oil phase were selected to prepare SLN. The influence of formulation, process variables on the preparation and quality of SLN were studied. Based on the investigation of single factors, orthogonal design was used to optimize SLN formulation and preparation process, and more, the reproducibility of the optimized results were studied.

RESULTSThe results showed that the device temperature (Ti), water temperature (Tw), and delivery rate (Rd) were the key factors that influence the preparation process of SLN, and Tw was extremely important. The ratio of microemulsion formulation, the ratio of microemulsion and distilled water had also influence on its quality.

CONCLUSIONMicroemulsion technique can be used to prepare solid lipid nanoparticles.

Alcohols ; Drug Carriers ; Emulsions ; Lipids ; chemical synthesis ; chemistry ; Nanotechnology ; Particle Size ; Phosphatidylcholines ; Solubility ; Technology, Pharmaceutical ; methods

Objective To study the effect of bromocriptine(BRC) on the activation of T lymphocyte stimulated by phytohemagglutinin(PHA).Methods After CD4+ T cell line Jurkat E6-1 cells were stimulated by PHA,prolactin(PRL) and BRC,respectively,the expression of linker for activation of T cells(LAT) and zeta-chain T cell receptor associated protein kinase 70 000(ZAP-70) mRNA of T lymphocytes were checked by RT-PCR.The expression of PRL mRNA of T lymphocytes was detected by Real time PCR.The expression of CD25(cluster of differentiation) as a marker of early activation on the surface of T lymphocytes was detected by flow cytometry,and the activation of nuclear factor-?B(NF-?B) was detected by luciferase reporter system.Results 1.BRC inhibited the expression of ZAP-70 as the common signal molecules both in the T lymphocyte activation pathway and PRL-prolactin-prolactin receptor(PRLR) signal transduction pathway,and decreased the expression of PRL mRNA produced by activation T lymphocytes.2.BRC enhanced the expression of LAT mRNA as another important signal molecular on the T lymphocytes and CD25 on the surface of the T lymphocytes.3.The activation of NF-?B of T lymphocytes was decreased.Conclusions BRC might inhibit the activation of T lymphocytes by inhibiting the expression of ZAP-70,the common signal molecules between T lymphocytes activation and PRL-PRL pathway,and PRL mRNA,the like-T lymphocyte growth factor.

OBJECTIVETo observe the distribution of the blood vessels in the integument tissue of the channel area of legs.

METHODSThe integument tissue of the lower limbs in the 12 cadavers were dissected with macro-and micro-dissection, radiographical technique of systemic artery and technique of image pattern analysis to observe and analyze the origins, branches and anastomoses in the integument tissues along the channels of legs.

RESULTSThe distributional density of the blood vessels in the integument tissues of legs along the channel area of the three-yin meridians of the foot, the Gallbladder Meridian, and the Urinary Bladder Meridian was higher than that in the other parts. They formed an obvious nutrient vascular chain on the arteriogram. The distributional density in the channel area of the Stomach Meridian was not obviously increased and the obvious nutrient vascular chain could not be seen.

CONCLUSIONAn obvious nutrient vascular chain is formed in the integument tissue along the channel area of legs except the Stomach Meridian.

Blood Vessels ; anatomy & histology ; Humans ; Leg ; blood supply ; Meridians