酮洛芬醇质体的制备、表征及其体外经皮渗透研究

制备酮洛芬醇质体并考察醇质体作为酮洛芬经皮给药载体的体外透皮特性。采用乙醇注入法制备酮洛芬醇质体,对其从粒径分布、Zeta电位值、包封率方面进行表征;用小鼠皮肤进行体外透皮试验,比较酮洛芬在乙醇溶液、脂质体以及醇质体中的透皮行为。结果表明,制得的酮洛芬醇质体平均粒径为166.0 nm,Zeta电位值为-56.70 m V,包封率为67.87%,12 h后皮肤累计渗透量显著高于酮洛芬脂质体和水溶液。因此,酮洛芬醇质体具有更好的透皮效果,值得进一步研究。     

酮洛芬醇质体的制备、表征及其体外经皮渗透研究

制备酮洛芬醇质体并考察醇质体作为酮洛芬经皮给药载体的体外透皮特性。采用乙醇注入法制备酮洛芬醇质体,对其从粒径分布、Zeta电位值、包封率方面进行表征;用小鼠皮肤进行体外透皮试验,比较酮洛芬在乙醇溶液、脂质体以及醇质体中的透皮行为。结果表明,制得的酮洛芬醇质体平均粒径为166.0 nm,Zeta电位值为-56.70 m V,包封率为67.87%,12 h后皮肤累计渗透量显著高于酮洛芬脂质体和水溶液。因此,酮洛芬醇质体具有更好的透皮效果,值得进一步研究。     

作为载体材料应用的明胶基复合材料研究进展

明胶由于其独特的性能广泛应用于制药工业,明胶作为载体材料在人体环境中易溶解,因此通常采用交联的方法与其他材料进行复合改性。本文从应用角度人手,对近年来明胶基复合材料的应用进行了综述。     

酰化皮明胶表面活性的研究

本文研究了以不同分子量的皮明胶和月桂酰氯为原料的酰化反应,并从产物的氨基取代度及其溶液的表面张力、起泡力、乳化力和去污力等性能,考察了反应原料配比对产物表面性能的影响。     

人参皂苷Rg3体外经皮渗透特性研究

研究人参皂苷Rg3体外经皮渗透特性以及不同促渗剂的影响。测定人参皂苷Rg3与经皮渗透相关的物理参数。通过扩散池试验,采用HPLC法测定人参皂苷Rg3的累积透过量(Q),拟合Q-t曲线,考察体外经皮渗透性能;测定β-环糊精、吐温-80、油酸、氮酮、薄荷油的增渗倍数(ER),考察不同促渗剂对人参皂苷Rg3经皮渗透性质的影响。人参皂苷Rg3的表观溶解度为66.70μg/mL,油水分配系数(logP)为2.63,熔点为312.2℃。人参皂苷Rg3经皮渗透为恒速过程;不同促渗剂对人参皂苷Rg3的促渗作用存在差异,薄荷油增渗倍数为2.38。人参皂苷Rg3体外释放符合零级过程,薄荷油对其促渗作用效果显著,可作为一种具有发展潜力的新型外用镇痛化合物。     

熊果苷经皮渗透及促渗透体系的初步研究

利用离体皮肤渗透技术研究了熊果苷的经皮渗透和几种渗透促进剂对其影响。结果表明,涂布量为80mg/cm^2,涂布面积为5cm^2时,熊果苷能经3天龄大鼠表皮和成年小鼠全皮渗透,渗透能力与浓度和作用时间有关。乳化体（霜）中熊果苷的渗透能力约为水溶液的50％,适当 透促进剂可提高能高熊果苷的渗透能力,如含水溶性氮酮的受试霜可提高20％。     

我国皮明胶的进展——祝明胶协会成立30周年

本文回顾了我国皮明胶的工艺与设备的进展。工艺方面的进步表现在:其一,碱法工艺的周期大为缩短;其二,我们曾经创造过高黏度时代,而现在又正在进军高冻力时代;其三,1980年代我们就已经实现了猪皮制革下脚料的酸法工业化生产,而牛皮制革下脚料的酸法生产则是由外资企业罗赛洛公司等在近年实施的;其四,用蓝矾皮生产高级工业胶我国已达到很高水平。设备方面的进步表现在:其一,原上海明胶厂王师俊1960～1970年代试制成功我国第一代明胶工业化设备;其二,1980年代国家机械工业部组织的国产现代化明胶设备攻关获得成功;其三,天津朱文烈1990年代试制成更适合我国明胶工业的现代化三效蒸发机;其四,2010年代出现了安徽风云公司的明胶浓缩膜与武汉张宇飞的明胶浓缩纳滤膜。     

三文鱼皮明胶的制备及其性能的研究

本文通过酸碱法对三文鱼皮进行预处理,制备了三文鱼皮明胶。研究分析了碱处理时间和浓度、酸处理时间和浓度对明胶产率和粘度的影响规律;测定了三文鱼皮明胶的成分、氨基酸组成、相对粘度。通过紫外光谱、红外光谱、X-射线衍射对其结构进行了分析。     

缓释药物载体明胶微球酸水解影响因素的研究

采用乳化交联法制备明胶微球(GMS),以柠檬酸为水解促进剂,利用双缩脲法研究了反应时间、温度及pH值对GMS及明胶水解程度的影响。结果表明,GMS水解的速率随反应时间的增长或温度的增高而加快,随水解pH值的增高而减慢;同等条件下,相比于GMS,明胶的水解较为彻底,在酸性环境中不如GMS稳定;GMS水解过程的SEM图进一步表明,在酸液的作用下,GMS溶胀后表面光滑致密,药物只能通过骨架缓慢扩散或交联结构的水解而缓慢释放,避免了药物突释。优化反应条件为:在水解时间3 h,温度80℃,pH值2时,GMS的水解较为彻底。     

谷氨酰胺转氨酶交联的原位明胶止血剂体外凝血实验的研究

目的:通过体外试管凝血实验,探讨自制谷氨酰胺转氨酶交联的原位明胶止血剂(HIGM)的凝血时间。方法:健康成年雄性杂种犬3只,每只动物股静脉取血后随机分为治疗组、阳性对照组和阴性对照组,治疗组加入HIGM、阳性对照组加入凝血酶和阴性对照组加入生理盐水。记录各组凝血时间、凝血块重量及颜色、体积,并进行组织病理学检查。共重复3次。结果:HIGM组凝血时间明显少于凝血酶组及空白组(P<0.01);HIGM组凝血块重量明显少于空白组(P<0.01),而与凝血酶相比无统计学意义(P>0.05)。与空白组及凝血酶组相比,HIGM组凝血块颜色较深,体积却与其它组的凝血块相当。结论:自制HIGM止血剂凝血时间较短,形成的凝血块质地紧实,为下一步体内实验提供了实验依据。     

Microwave‐Assisted Preparation of Hydrogel‐Forming Microneedle Arrays for Transdermal Drug Delivery Applications

A microwave (MW)‐assisted crosslinking process to prepare hydrogel‐forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether‐alt‐maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW‐assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm^?1). It was shown that, by using the MW‐assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW‐prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.

     

Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.     

Functional Properties of Two-Component Hydrogel Systems Based on Gelatin and Polyvinyl Alcohol—Experimental Studies Supported by Computational Analysis

The presented research is focused on an investigation of the effect of the addition of polyvinyl alcohol (PVA) to a gelatin-based hydrogel on the functional properties of the resulting material. The main purpose was to experimentally determine and compare the properties of hydrogels differing from the content of PVA in the blend. Subsequently, the utility of these matrices for the production of an immobilized invertase preparation with improved operational stability was examined. We also propose a useful computational tool to predict the properties of the final material depending on the proportions of both components in order to design the feature range of the hydrogel blend desired for a strictly specified immobilization system (of enzyme/carrier type). Based on experimental research, it was found that an increase in the PVA content in gelatin hydrogels contributes to obtaining materials with a visibly higher packaging density, degree of swelling, and water absorption capacity. In the case of hydrolytic degradation and compressive strength, the opposite tendency was observed. The functionality studies of gelatin and gelatin/PVA hydrogels for enzyme immobilization indicate the very promising potential of invertase entrapped in a gelatin/PVA hydrogel matrix as a stable biocatalyst for industrial use. The molecular modeling analysis performed in this work provides qualitative information about the tendencies of the macroscopic parameters observed with the increase in the PVA and insight into the chemical nature of these dependencies.     

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.     

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.