Comparative lyophilized platelet-rich plasma wafer and powder for wound-healing enhancement: formulation,in vitro and in vivo studies

Platelet-rich plasma (PRP) accelerates wound healing, as it is an excellent source of growth factors. PRP was separated from whole human blood by centrifugation. PRP powder and wafers were prepared by lyophilization, with the wafers prepared using sodium carboxymethylcellulose (Na CMC). The PRP wafers showed porous structures, as indicated by scanning electron microscopy (SEM) images, and the ability of the wafer to absorb exudates and thus promote wound healing was tested with the hydration capacity test. The platelet count was tested and indicated that the presence of PRP in the wafers had no effect on the platelet count. An antimicrobial activity test was carried out, showing that PRP had antibacterial activity against Gram-negative bacteria. Compared with lyophilized PRP powder and PRP-free wafers, PRP wafers showed the highest percent of wound size reduction on induced wounds in rats. Histopathological examination of rat skin showed that the PRP wafers achieved the shortest healing time, followed by the lyophilized PRP powder and finally the PRP-free wafers. The present study revealed that PRP can be formulated as a wafer, which is a promising pharmaceutical delivery system that can be used for enhanced wound-healing activity and improved the ease of application compared to lyophilized PRP powder.     

Preparation and Characterization of Nanoliposomes Entrapping Medium-Chain Fatty Acids and Vitamin C by Lyophilization

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes.     

丝素/明胶/壳聚糖支架材料的构建及表征

基于丝素、明胶和壳聚糖三者作为生物材料的优良性能,采用二次冷冻干燥方法制备了一种疏松多孔的新型组织工程材料。首先检测了复合支架材料的理化性能,其次研究了该材料的形貌结构,最后利用细胞学和动物学实验对该材料的细胞毒性和生物相容性进行了评价。结果显示,复合支架材料孔隙率高于(53.52±1.16)%,吸水率高于(89.36±0.43)%。在预冻温度为-20 ℃,以戊二醛作交联剂,丝素/明胶/壳聚糖复合比例为1∶1∶1.5时,制备的材料力学性能达到最优,断裂伸长率为(11.5±1.05)%。扫描电镜图显示该材料具有连通的三维多孔结构。红外光谱及X射线衍射表明材料各组分化学基团间发生了相互作用,并伴有结晶状态的改变。小鼠体内植入实验表明,该支架无毒、生物相容性好,是一种综合性能优异的组织工程材料。     

Development of In Situ Gelling Inserts by Lyophilization for Nasal Delivery of Terbutaline Sulfate

The aim of present study was development and in vitro characterization of sponge like, in situ gelling inserts of terbutaline sulfate by lyophilization for nasal administration to avoid first-pass metabolism. The inserts were investigated for thickness, water uptake, moisture absorption, drug content, in vitro drug release, histopathology, scanning electron microscopy analysis, and powder X-ray diffraction. The developed inserts were smooth in appearance with uniform thickness and drug content. The inserts exhibited satisfactory water uptake and extended drug release up to 10?h. Hence, inserts could be used as a viable alternative to improve therapeutic efficacy of terbutaline sulfate.     

Characterization of the mass transfer of lyophilized products based on X-ray micro-computed tomography images

ABSTRACT

This paper proposes a systematic work process for the rapid determination of resistance to vapor flow given by the products being freeze-dried. This approach couples mathematical modeling and 3D nondestructive X-ray imaging to reconstruct the internal structure of lyophilized samples. Knowledge of the internal structure is fundamental to better understand the relationship between freezing and within-product heterogeneity as well as between freezing and the drying behavior of the product being lyophilized. The method was validated upon mannitol-based formulations using various freezing protocols. This stepwise approach was demonstrated to be helpful to lyophilization professionals for the control of within-product heterogeneity and for the optimization of the cycle.     

Effect of freeze-drying process on the physical stability and properties of Voriconazole complex system

This paper studied the effect of lyophilization together with annealing on the physical properties, such as critical micelle concentration, particle size, differential scanning calorimetry, and eutectic point. The freeze-drying method had successfully set up the Voriconazole complex system. Samples processed by lyophilization had slightly superiority compared to those without the lyophilization in terms of surface properties. Furthermore, this paper also investigated the physical stabilities of Voriconazole complex system related to cloud point thermodynamic and insoluble particles. Samples processed by lyophilization with annealing achieved better performance of physical stabilities than those without any process.     

Effect of drying technique on some physical properties of cross-linked high amylose/pectin mixtures

Polymers mixtures as well as cross-linking reactions are approaches that have been used successfully to modulate the polymers characteristics in order to improve the control over drug release rate. High amylose and pectin are polysaccharides frequently used to prepare drug delivery systems. Since the drying technique can strongly influence the properties of such systems, the aim of this work was to characterize high amylose/pectin mixtures cross-linked with sodium trimetaphosphate and dried by different techniques – oven and lyophilization. The results showed that samples dried by lyophilization presented reduced particle size, higher porosity and higher swelling ability than the samples dried in oven. Besides, lower thermal stability and different diffraction patterns showed by the former particles should reflect the structural changes as a function of drying technique.     

Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

Rifampicin-loaded poly(ε-caprolactone)–b-poly(ethylene glycol)–poly(ε-caprolactone) flower-like polymeric micelles display low aqueous physical stability over time and undergo substantial secondary aggregation. To improve their physical stability, the lyoprotection–lyophilization process was thoroughly characterized. The preliminary cryoprotectant performance of mono- and disaccharides (e.g. maltose, glucose), hydroxypropyl-β-cyclodextrin (HPβCD) and poly(ethylene glycol) (PEG) of different molecular weights was assessed in freeze–thawing assays at −20°C, −80°C and −196°C. The size and size distribution of the micelles at the different stages were measured by dynamic light scattering (DLS). A cryoprotectant factor (f_c) was determined by taking the ratio between the size immediately after the addition of the cryoprotectant and the size after the preliminary freeze–thawing assay. The benefit of a synergistic cryoprotection by means of saccharide/PEG mixtures was also assessed. Glucose (1 : 20), maltose (1 : 20), HPβCD (1 : 5) and glucose or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio) were the most effective systems to protect 1 per cent micellar systems. Conversely, only HPβCD (1 : 5) cryoprotected more concentrated drug-loaded micelles (4% and 6%). Then, those micelle/cryoprotectant systems that displayed f_c values smaller than 2 were freeze-dried. The morphology of freeze-dried powders was characterized by scanning electron microscopy and atomic force microscopy and the residual water content analysed by the Karl Fisher method. The HPβCD-added lyophilisates were brittle porous cakes (residual water was between 0.8% and 3%), easily redispersable in water to form transparent systems with a minimal increase in the micellar size, as determined by DLS.     

嗜酸乳杆菌泠冻干燥过程中保护剂的选择

采用不同保护剂组合，对嗜酸乳杆菌在冷冻干燥中存活率进行了测定。结果表明，保护剂对提高冻干过程中嗜酸乳杆菌的存活率具有明显效果，且组合不同保护剂协同累加效果不同，其中10％脱脂乳 10％乳糖La-1和La-2的存活率均为100％。     

直投式酸奶发酵剂的商品化生产研究

通过对不同保加利亚乳杆菌与嗜热链球菌菌株的酸化活力、黏度、蛋白水解能力和共生能力等生理学指标的测定,筛选出4对适于发酵生产用的菌株组合,并以菌株Y6+ST1作为进一步研究对象,获得其最佳增殖培养基为番茄汁为2.5%,乳糖为1.0%,酵母膏为0.5%,蛋白胨为1.5%,42℃培养6h后其活菌数达到1.4×109mL-1;Y6+ST1组合的最佳保护剂组成为脱脂奶粉为18.0%,甘油为2.0%,谷氨酸钠为1.0%和吐温-80为0.5%,经冷冻干燥后其活菌数达到3.62×1011g-1。该组合工业化生产的最佳工艺参数是培养温度42.3℃,pH值为6.4,搅拌转速86.8r/min和3%的接种量,1.0%补料(脱脂乳),发酵时间6h;-40℃,15h后,最终冷冻干燥产品活菌数为1011g-1。