Controlled release of heparin from blended polyurethane and silk fibroin film

Polyurethane was blended with silk fibroin and heparin to prepare a heparin-releasing system. The release rate and the percentage of the cumulative amount of the released heparin can be controlled by the loading amount of heparin in the film, the composition ratio of silk fibroin to polyurethane, and the thickness of the film. The slower and more sustained release of heparin can be obtained by increasing the film thickness, the loading amount of heparin and the content of silk fibroin in the film. Thus the high bioactivity and long lasting antithrombogenicity of the raw heparin can be maintained for the blended film. The coagulation time tests showed that the composite film had good blood compatibility.     

可注射原位凝胶的制备及性能表征

以聚琥珀酰亚胺(PSI)为原料,利用酰亚胺基开环反应,首先制备得到α,β-聚(N-羟乙基)-DL-天门冬酰胺(PHEA),再与丙烯酰氯反应,制备得到接枝丙烯酰胺基α,β-聚(N-羟乙基)-DL-天门冬酰胺(PHA).通过FT-IR、NMR对其结构进行了表征.这种大分子单体的溶液可在人体温度下发生原位的交联反应,形成凝胶.可通过改变接枝率、大分子单体浓度等因素控制凝胶化时间.当选用质量浓度为0.1g/mL的PHA1#(接枝率为19.6%)单体、交联剂质量浓度为4mg/mL、引发剂浓度为20mmol/L时,凝胶化时间为90s.该凝胶具有可注射性和疏松的大孔结构,并且凝胶化时间可控,在模拟体液中有轻微溶胀,是较理想的治疗干眼症注射式材料.     

Surface sulfonation of silk fibroin film by plasma treatment and in vitro antithrombogenicity study

To improve the blood compatibility of Bombyx mori silk fibroin (SF) film, the film was modified by SO₂ gas plasma treatment, or by a two-step process including NH₃ gas plasma treatment and reaction with 1,3-propane sultone. XPS and ATR-FTIR were used to analyze the surface chemical elements. In vitro antithrombogenicity was determined by the method of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) tests. Percents of sulfur element on the surfaces of both modified SF films were 4.03% and 3.30%, respectively, while that of the control film was only 0.32%. Moreover, the antithrombogencity of treated films was increased remarkably due to surface sulfonation. The results implied a potential use of sulfonated SF for blood-contacting biomaterials.     

同轴静电纺再生丝素/丝胶蛋白纤维的制备及其形态结构表征

模仿蚕丝的组成和结构,利用同轴静电纺丝法制备了以再生丝素蛋白（RSF）为＂芯＂、丝胶蛋白（SS）为＂皮＂的双组分静电纺纤维。通过扫描电镜和透射电镜研究了内层纺丝液流速（Qc）、电压（U）、接收距离（D）以及场强（E）等参数对同轴静电纺RSF/SS纤维形态结构的影响。研究结果表明纤维的平均直径在1400～2100nm左右,皮-芯层结构清晰;Qc对纤维皮-芯层结构的影响较大,过大的内层纺丝液流速会因外层丝胶对内层丝素的包裹不均匀而导致偏芯现象;随E的增加（U增加或D减小）,纤维的直径及其分布显著减小,皮-芯层结构清晰;相同E下,高电压、长距离利于纤维的细化,使直径变细且分布均匀,皮-芯层结构明显。     

双氯灭痛壳聚糖水凝胶微球的制备及其性能研究

在Span80与植物油形成的反相胶束体系中,通过戊二醛交联制备出壳聚糖水凝胶微球(CHM)。采用红外光谱和透射电镜等方法对CHM结构及粒子形态进行了研究。同时对CHM的溶胀度及其对模型药物双氯灭痛的体外释放行为进行了考察。结果表明,CHM具有较好的控制药物释放的作用。交联程度对微球粒径、溶胀度及药物释放性能影响较大。     

Preparation and cytocompatibility of silk fibroin/chitosan scaffolds

One challenge in soft tissue engineering is to find an applicable scaffold, not only having suitable mechanical properties, porous structures, and biodegradable properties, but also being abundant in active groups and having good biocompatibility. In this study, a three-dimensional silk fibroin/chitosan (SFCS) scaffold was successfully prepared with interconnected porous structure, excellent hydrophilicity, and proper mechanical properties. Compared with polylactic glycolic acid (PLGA) scaffold, the SFCS scaffold further facilitated the growth of HepG2 cells (human hepatoma cell line). Keeping the good cytocompatibility and combining the advantages of both fibroin and chitosan, the SFCS scaffold should be a prominent candidate for soft tissue engineering, for example, liver.     

Small-diameter vascular grafts of Bombyx mori silk fibroin prepared by a combination of electrospinning and sponge coating

The present study aimed to produce small-diameter grafts made of a silk fibroin by electrospinning. In order to reinforce the electrospun silk fibroin graft (ES), the graft was coated with a silk sponge (ESSC). Physical properties such as a diameter of the electrospun silk fibers were influenced by a concentration of fibroin solution. Ultimate tensile strength (UTS) of the ESSC graft was improved compared to the ES graft. However, the ESSC graft was less compliant than the ES graft. Importantly, water permeability of the ESSC graft was within the range of which endothelialization was promoted in previous studies.     

Evaluation of dibutyrylchitin as new excipient for sustained drug release

Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and ¹H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.     

Preparation and characterization of amphotericin B-loaded silk fibroin nanoparticles-in situ hydrogel composites for topical ophthalmic application

Journal of Materials Science - The objective of this study was to develop and characterize a novel combined systems of amphotericin B-loaded silk fibroin nanoparticles (AmB-FNPs) and in situ...     

Fabrication and characterization of fibroin solution and nanoparticle from silk fibers of Bombyx mori

The present investigation aims to study the effect of degumming time on the structural property of silk fiber obtained by silk cocoons of Bombyx mori, followed by preparation of the regenerated silk fibroin (RSF) solution which can be subsequently molded into silk nanoparticles. Silk fibers degummed with different media at different time intervals were investigated for the degumming loss and were characterized using Ffourier transform infrared (FTIR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Maximum degumming was observed when the fibers were treated with sodium carbonate for 60 min. SEM and atomic force microscopy (AFM) images of RSF solution showed aggregation of silk globules resulting in formation of solvated macrochains and giving it an appearance of island-like morphology. Blank silk nanoparticles prepared from the RSF solution showed a smooth and spherical surface devoid of any adhesion using SEM, AFM, and transmission electron microscopy (TEM). The prepared silk nanoparticles may further be explored for loading drug entities and targeting.     

Optical and photocatalytic properties of sulfide semiconductor quantum dots (QDs) synthesized by silk fibroin template

Bio-template method is a simple, controllable and environmental friendly strategy to synthesize nanomaterials. It also avails the formation of bioactive and biocompatible nanoparticle–biomolecule hybrid for biotechnical applications. In this paper, silk fibroin was first successfully used as biomolecule template for the biomimic synthesis of CdS and ZnS quantum dots (QDs). The QDs showed promising applications as fluorescence probes and nanocatalysts. The effect of preparation situation to their optical and photocatalytic properties was well researched and CdS QDs with satisfying catalytic activities could be achieved by adjusting the protein matrix. It offers us a low-cost and effective way to synthesize series of sulfide semiconductor nanomaterials using silk fibroin.     

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug

Objective: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug.

Methods: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG).

Results: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2?µm. The tablets prepared for WG disintegrated in time less than 30?min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC.

Conclusion: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.     

Surelease as granulating liquid in preparation of sustained release matrices of ethylcellulose and theophylline

Objectives: Use of Surelease as a granulation liquid in preparation of granules and matrices of theophylline and ethylcellulose was evaluated.

Materials and methods: Physical mixtures (at 1:1 or 1:1.5 drug:polymer) were granulated using water, Surelease or diluted Surelease as granulating liquid. The granule characteristics (shape, size, flow rate, mechanical properties, friability and release profile) were studied. Afterwards, matrices were manufactured and their crushing strengths, friability and release profiles were determined.

Results: Granulation produced agglomerated particles with better flowability than physical mixtures. Change of granulation liquid from water to Surelease or diluted Surelease led to the marginal increase in size of granules at 1:1 drug:polymer, however, the flow rate and Carr’s index were considerably improved. The hardness, elastic modulus, friability and rate of drug release were not affected by granulation liquid. Increase in polymer content resulted in reduction in size of granules, flow rate, elastic modulus and rate of drug release. However hardness of the granules was unaffected. Granulation process and granulation liquid did not affect the hardness, and dissolution rate of matrices at 1:1 drug:polymer, while the use of Surelease or diluted Surelease as a granulating liquid, increased the hardness and decreased drug release rate at 1:1.5 drug:polymer. Matrices prepared from Surelease or diluted Surelease showed similar characteristics.

Conclusions: Surelease is a suitable granulating liquid for preparation of ethylcellulose matrices especially when high amount of polymer is used and could not only improve the flow and compatibility of the granules, but also help in reducing the rate of drug release.     

Formulation and development of orodispersible sustained release tablet of domperidone

Abstract

Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug, but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30?seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200?μm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner’s ratio of the blend for compression showed good flowability and high percent compressibility. The optimized ODT-SR showed disintegration time of 21?seconds and matrix controlled drug release for 9?h. In-vivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16?h as compared 3.86?h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation.     

A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.

Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol^® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.

Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f₂ > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC_0–36 and C_max ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.

Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol^® SR capsule.     

Preparation and characterization of regenerated fiber from the aqueous solution of Bombyx mori cocoon silk fibroin

The regenerated silk fibers with high strength and high biodegradability were prepared from the aqueous solution of Bombyx mori silk fibroin from cocoons with wet spinning method. Although the tensile strength of the regenerated silk fibroin fiber, 210 MPa is still half of the strength of native silk fiber, the diameter of the fiber is about 100 μm which is suitable for monofilament of suture together with high biodegradability. The high concentration (30%, w/v) of the aqueous solution of the silk fibroin which corresponds to the high concentration in the middle silkgland of silkworm was obtained. This was performed by adjusting the pH of the aqueous solution to 10.4 which corresponds to pK_a value of the OH group of Tyr residues in the silk fibroin. The mixed solvent, methanol/acetic acid (7:3 in volume ratio) was used as coagulant solvent for preparing the regenerated fiber. The structural change of silk fibroin fiber by stretching was monitored with both ¹³C solid state NMR and X-ray diffraction methods, indicating that the high strength of the fiber is related with the long-range orientation of the silk fibroin chain with β-sheet structure.     

空心羟基磷灰石亚微球/壳聚糖可注射水凝胶的制备及表征

采用W/O/W复乳法制备空心羟基磷灰石(HAP)亚微球,将空心HAP亚微球均匀分布在壳聚糖/甘油磷酸钠(CS/GP)体系中制备可注射HAP/CS水凝胶(gel 1),同时制备可注射CS水凝胶(gel 2).用X射线衍射仪、场发射透射电镜、红外光谱、扫描电镜对空心HAP亚微球和水凝胶进行了表征,并比较分析了两种溶胶的成胶...     

TiO2共混丝朊接枝聚丙烯腈过滤膜制备及性能研究

针对传统高分子过滤膜使用有机溶剂易造成环境污染的问题,以氯化锌水溶液为溶剂,丝朊均相接枝聚丙烯腈,加入纳米TiO2得到铸模液,以水为凝固浴,制备TiO2共混的丝朊接枝聚丙烯腈(SF-g-PAN/TiO2)过滤膜。通过扫描电子显微镜,红外光谱等方法对膜进行表征,研究不同TiO2含量的SF-g-PAN过滤膜的亲水性、抗污染性能、力学性能以及SF-g-PAN/TiO2膜对不同分子量染料的截留。结果表明:随着TiO2含量的增加,膜的力学强度先增大后减小。TiO2含量为1%(质量分数)时,膜的力学和抗污染性能最好;在0.10 MPa下,SF-g-PAN/TiO2膜对于分子量大于660的染料截留率为96%以上,通量达到80 L/(m^2·h)。     

Preparation and in vitro/in vivo evaluation of a ketoprofen orally disintegrating/sustained release tablet

Context: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time. Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs.

Methods: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs). Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000. The optimal parameters of spray drying were 100°C for inlet air temperature and 1.5 mL/min for feed rate. Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP). The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated.

Results: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s. Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets. Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets. In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules.

Conclusion: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.     

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol–solvent–water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48?h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.