Low-temperature aerosol flow reactor method for preparation of surface stabilized pharmaceutical nanocarriers

Nanoparticles can be used to improve the delivery of many drugs, especially peptides and proteins. Although several methods are available for polymeric nanoparticle preparation, there are few single-stage processes that produce dry, solid nanoparticles that can be easily re-dispersed in pharmaceutical vehicles. The aerosol flow reactor method is a single-stage process that has been used for the preparation of multicomponent, coated nanoparticles under uniform temperature and gas flow field. However, it is traditionally used with high synthesis temperatures. In the present study, the aerosol flow reactor method was further optimized for processing and surface stabilization of pharmaceutical nanoparticles containing temperature sensitive biomolecules. In the developed method, drug-loaded carrier nanoparticles consisting of a biodegradable polymer (Eudragit L100) and a drug (phenylephrine hydrochloride) were first produced by aerosol droplet drying and subsequently coated in the gas phase. The carrier particles were coated with l-leucine in order to inhibit agglomeration of the nanoparticles in solutions before administration. In the coating process, a side stream of l-leucine vapor was directed into the main aerosol flow containing the drug-loaded carriers. The mixing with the main flow at ambient temperature induced a supersaturation of l-leucine vapor and condensation on the carrier particles. The results demonstrate that solid, hydrodynamically stable drug-loaded polymeric nanoparticles can be produced with a thin l-leucine coating. The low process temperature enables the surface engineering of particles loaded with temperature sensitive drugs or bioactive materials to be utilized for drug delivery purposes.     

静电纺丝制备聚己内酯载药纤维工艺参数研究

选用聚己内酯作为载体材料、5-氟尿嘧啶作为承载药物,研究了静电纺丝过程中纺丝液浓度、纺丝电压及收集距离对纤维直径的影响,对制备的聚己内酯载药纤维膜进行元素检测分析及力学性能测试,通过体外药物释放实验,验证了聚己内酯载药纤维膜药物控释的效果.结果表明,随着纺丝液的浓度和收集距离增加,纤维的平均直径增大;随着纺丝电压增加,...     

Electrospun polymeric nanofibers for dental applications

Electrospinning is an economical, efficient, and versatile process for the preparation of continuous nanofibers with desired patterns, tailored fiber diameters, and orientations. Since its invention, electrospinning has been utilized to prepare nanofibers from several natural polymers and synthetic polymers for use as scaffolds in tissue engineering, regeneration, and biomedical applications. Furthermore, complex scaffolds were prepared by electrospinning complex polymer solutions formulated by blending natural and synthetic organic polymers with bioceramics and other inorganic molecules. Lately, coaxial electrospinning has emerged as a promising technology in the preparation of drug-loaded biodegradable core-shell structured micro/nanofibers for sustained drug delivery applications. This paper will discuss the basic mechanism of electrospinning, parameters governing the electrospinning process, various materials investigated for use in the electrospinning process, and its recent advances.     

Release characteristics of four model drugs from drug-loaded electrospun cellulose acetate fiber mats

Ultra-fine fiber mats of cellulose acetate (CA; M_w ≈ 30?000 Da; degree of acetyl substitution ≈ 2.4) containing four different types of model drugs, i.e., naproxen (NAP), indomethacin (IND), ibuprofen (IBU), and sulindac (SUL), were successfully prepared by electrospinning from 16% w/v CA solutions in 2:1 v/v acetone/N,N-dimethylacetamide (DMAc). The amount of the drugs in the solutions was fixed at 20 wt.% based on the weight of CA powder. The morphology of the drug-loaded electrospun (e-spun) CA fiber mats was smooth, with the average diameters of these fibers ranging between 263 and 297 nm. No presence of the drug aggregates of any kind was observed on the surfaces of these fibers, suggesting that the drugs were encapsulated well within the fibers. After submersion in the acetate buffer solution at 37 °C for 24 h, the drug-loaded e-spun CA fiber mats swelled particularly well (i.e., 570-630%), while the corresponding solvent-cast film counterparts did not. The release characteristics of the model drugs from both the drug-loaded CA fiber mats and the drug-loaded as-cast CA films were carried out by the total immersion method in the acetate buffer solution at 37 °C. At any given immersion time point, the release of the drugs from the drug-loaded e-spun CA fiber mats was greater than that from the corresponding as-cast films. The maximum release of the drugs from both the drug-loaded fiber mats and films could be ranked as follows: NAP > IBU > IND > SUL.     

Fabrication and characterization of dual drug-loaded poly (lactic-co-glycolic acid) fiber-microsphere composite scaffolds

The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06?g/mL; applied voltage: 15?kV; and flow rate: 0.6?mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies.     

Controlled fabrication of drug-loaded protein nanoparticles via flash nanoprecipitation

Protein nanoparticles (NPs) are perspective vehicles for delivery of therapeutic agents. However, whether they will ever reach the stage of widespread application relies crucially on the development of reliable fabrication strategies and techniques. Herein, we report a continuous precipitation approach, namely flash nanoprecipitation (FNP) for efficient construction of drug-loaded protein NPs with regulated size and properties. Our design relies on rapid mixing of solvent streams containing drug and protein with anti-solvent streams which triggers co-precipitation of the solutes and creates NPs by controlled nucleation and growth. The established process is generally capable for controlled formulation of diverse drug-loaded protein NPs. Our results validate the distinctive advantages of FNP over conventional precipitation approaches, including fast process, continuous production and excellent control of product size and properties. FNP is therefore likely to be the method of choice for preparing nanosized dispersions of hydrophobic drugs or food additives on an industrial scale.     

超声诊疗一体化的载药壳聚糖纳米微泡的制备

载药微泡在超声诊疗一体化中具有广阔的应用前景.以壳聚糖为原料制备了一种能够实现超声诊疗一体化功能的载药壳聚糖纳米微泡,采用激光粒度仪、透射电镜、扫描电镜、紫外分光光度计、超声成像仪以及圆二色谱仪等对载药纳米微泡进行表征,研究了载药纳米微泡的稳定性,并验证了其体外超声显影和超声释放的能力.结果 表明,载药纳米微泡平均粒径...     

Electrospun Methacrylate-Based Copolymer/Indomethacin Fibers and Their Release Characteristics of Indomethacin

Three methacrylate-based copolymers [i.e., poly(methacrylic acid-co-methyl methacrylate) (E-L100), poly(ethyl acrylate-co-methyl methacrylate-co-trimethyl-ammonioethyl methacrylate chloride) (E-RLPO), and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) (E-EPO)] were successfully electrospun into fibers, using ethanol (EtOH) as the spinning solvent. However, electrospinning of these methacrylate-based copolymers and indomethacin (10% by weight of the copolymer) was only successful when an equivolume of EtOH and ethylacetate (EA) was used as the co-solvent system. The drug-loaded as-spun copolymeric fibers appeared to be flat, with the size ranging between 1.2 and 2.5 μm. At 24 h, the amount of the drug released from these drug-loaded as-spun copolymer fibers was about 55%, 30%, and 18% for drug-loaded as-spun E-EPO, E-L100, and E-RLPO fibers, respectively.     

A Novel Strategy as a Potential Rapid Therapy Modality in the Treatment of Corneal Ulcers: Fluconazole/Vancomycin Dual Drug-Loaded Nanofibrous Patches

Corneal ulcer, which is brought on by a breach in the epithelial barrier, is a dangerous infection of the avascular corneal stroma. New treatment strategies are needed, suppressing the aggressive nature of the disease and including a combination of different drugs. In this study, vancomycin (VAN) and fluconazole (FLU) dual-drug loaded dual-layered polyvinyl alcohol and gelatin (PVA/GEL) nanofibrous patches are produced by electrospinning. Scanning electron microscopy (SEM) images show smooth surfaces are obtained for both pure and drug-loaded nanofibrous patches. The tensile test results report that loading the FLU and VAN separately into the PVA/GEL patches decrease both the tensile strength and elongation at break and it is further reduced when combining two drug-loaded layers in one patch. According to drug release results, the FLU and VAN-loaded nanofibrous patches show a controlled release profile extending up to 96 h. Moreover, PVA/GEL/FLU, PVA/GEL/VAN, and PVA/GEL/FLU/VAN nanofibrous patches display significant antimicrobial activity against Candida albicans and Staphylococcus aureus. SEM, 4'-6diamidynofenyloindol (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay show that PVA/FLU and PVA/GEL/FLU/VAN nanofibrous patches have a superior effect on NIH3T3 cell spreading and proliferation. The novelty of this study lays in the development of a potential dual drug rapid treatment for corneal ulcers of aggressive nature.     

Electrospun Nanofibers: Materials,Synthesis Parameters,and Their Role in Sensing Applications

Since the last decade, electrospinning is garnering more attention in the scientific research community, industries, applications like sensing (glucose, H₂O₂, dopamine, ascorbic acid, uric acid, neurotransmitter, etc.), biomedical applications (wound dressing, wound healing, skin, nerve, bone tissue engineering, and drug delivery systems), water treatment, energy harvesting, and storage applications. This review paper provides a brief overview of the electrospinning method, history of the electrospinning, factors affecting the electrospun nanofibers, and their morphology with different materials and composites (metals, metal oxides, 2D material, polymers and copolymers, carbon-based materials, etc.) used in the electrospinning technique with optical spinning parameters. Moreover, this paper deliberates the application of electrospun nanofibers and fibrous mats for sensing (electrochemical, optical, fluorescence, colorimetric, mechanical, photoelectric, mass sensitive change, resistive, ultrasensitive, etc.) in most illustrative representations. In the end, the challenges, opportunities of the electrospun nanofibers, and new direction for future progress are also discussed.     

PVA/PAA-Based Antibacterial Wound Dressing Material with Aloe Vera

The incorporation of drugs into the dressings make these dressings antimicrobial and help in control of infection around the wound. The wound dressing materials based on PVA/PAA, ciprofloxacin HCl, and aloe vera have been designed and developed so that the wound undergoes proper healing and scar formation is minimal. These wound dressing materials are produced using the electrospinning method. The wound dressing materials are characterized using the FT-IR, DSC, DTA, TGA, and SEM techniques. The wound dressing materials are tested for microbial activity tests and drug release experiments. Controlled ciprofloxacin HCl release is observed.     

Effect of anionic/siloxy groups on the release of ofloxacin from soft contact lenses

For the treatment of ocular diseases, chemotherapeutic antibiotics, for example, Ofloxacin, are usually administrated through the application of eye drops during ophthalmic perioperative sterilization. However, this approach has several drawbacks, such as the need for frequent application caused by tears draining the drugs out of the eyes or the presence of a possible contraindication of eye drops when contact lenses are worn. To overcome these problems, we have studied contact lenses composed of hydrogels, which function as a type of drug delivery system technology. We synthesized hydrogels to be used as contact lenses with sufficient amounts of drug uptake and release profiles for sterilization treatment during the perioperative period in ophthalmic areas. This study showed that the hydrogels that included side‐chain ionic groups and silyl groups were useful materials to prepare drug delivery contact lenses. The ionic groups in the hydrogels could functionally retain a drug if an ionic substituent was present. It is noteworthy that the drug content in the contact lenses could readily be controlled by changing the ratio of ionic monomer contents during polymerization. Furthermore, the controlled drug release of silyl‐group‐containing hydrogels showed sustained release over 72 h, which indicated that the hydrogels could be used as contact lenses for sustained drug release. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2013     

含紫杉醇PLGA缓释微球的研制及理化性质

目的研制含紫杉醇的聚乳酸和乙醇酸的共聚物[Poly(lactic-co-glycolic acid),PLGA]生物可降解高分子微球,并对其药物释放动力学进行分析。方法使用相对分子质量为20000的PLGA作为造粒对象,对不同溶剂的PLGA溶液进行喷雾化造粒,以优化出最佳造粒参数。在此条件下对含紫杉醇的PLGA溶液进行喷雾化造粒,制备紫杉醇/PLGA微球。结果形成单分散粒子的条件是较高的应用电压和较低的溶液流率,5%(wt)的PLGA溶液浓度溶于5∶1的氯仿和DMF的混合溶剂(v/v)中。在优化的喷雾参数下,得到了粒径均一、直径为300nm的单分散载紫杉醇的PLGA微粒。当紫杉醇在微球中含量较低时(2%),药物释放呈零级释放模式。较高的载药浓度(>5%)会在初期有轻微药物突释,然后呈零级释放模式。结论电喷雾化技术制备载药微粒是简单可行的新制药技术。含紫杉醇的PLGA微粒有望成为新一代抗癌药物剂型。     

Dual Drug Release Electrospun Core-Shell Nanofibers with Tunable Dose in the Second Phase

This study reports a new type of drug-loaded core-shell nanofibers capable of providing dual controlled release with tunable dose in the second phase. The core-shell nanofibers were fabricated through a modified coaxial electrospinning using a Teflon-coated concentric spinneret. Poly(vinyl pyrrolidone) and ethyl cellulose were used as the shell and core polymer matrices respectively, and the content of active ingredient acetaminophen (APAP) in the core was programmed. The Teflon-coated concentric spinneret may facilitate the efficacious and stable preparation of core-shell nanofibers through the modified coaxial electrospinning, where the core fluids were electrospinnable and the shell fluid had no electrospinnability. The resultant nanofibers had linear morphologies and clear core-shell structures, as observed by the scanning and transmission electron microscopic images. APAP was amorphously distributed in the shell and core polymer matrices due to the favorite second-order interactions, as indicated by the X-ray diffraction and FTIR spectroscopic tests. The results from the in vitro dissolution tests demonstrated that the core-shell nanofibers were able to furnish the desired dual drug controlled-release profiles with a tunable drug release amount in the second phase. The modified coaxial electrospinning is a useful tool to generate nanostructures with a tailored components and compositions in their different parts, and thus to realize the desired functional performances.     

Freeze-drying of liposomal nanohybrid cerasomes with cryoprotectants: In vitro and in vivo evaluation

Liposomal nanohybrid cerasomes as a new type of drug carrier has been widely applied in the controlled release of drugs. However, such vesicles containing polysiloxane networks on the surface were liable to aggregate during the process of freeze-drying for routine storage. To solve this problem, several previously reported cryoprotectants including sucrose, mannitol, sodium alginate, and glucose were chosen for protecting the 10-hydroxycamptothecin-loaded liposomal nanohybrid cerasomes (The drug encapsulation efficiency was of 67.31?±?7.42% and the drug loading content was of 6.73?±?0.74%.) in freeze-drying process. It was found that liposomal nanohybrid cerasomes treated with mannitol can be well dispersed, and the results of particle size and zeta potential showed that the drug-loaded vesicles were well protected with mannitol. In vitro drug release and in vivo pharmacokinetic study showed that the optimal addition amount of mannitol was twice the mass of the drug-loaded vesicles, whereby the cumulative release profile and the pharmacokinetic parameters were similar in the freeze-dried and fresh vesicles.     

载双组分药物磷酸钙骨水泥的性质和体外释放

为了研究载双组分药物磷酸钙骨水泥(calcium phosphate cement,CPC)的性质和药物释放行为,以对乙酰氨基酚和氯霉素为药物模型,制备载双组分药物的CPC。用Gilmore双针法、X射线衍射、红外光谱分析以及紫外-可见分光光度计等研究双组分药物对CPC的凝固时间和相成分的影响以及其药物释放行为。结果表明:药物的载入延长CPC的凝固时间;延迟CPC向羟基磷灰石转化,但不会改变其终产物的成分;两种药物可以独立释放,但双组分组的释药速率低于单组分组的,释放均基本吻合Higuchi扩散释放模型。     

含氯化钠的聚乙烯醇静电纺丝研究

研究了不同聚合度聚乙烯醇与少量氯化钠盐混合物水溶液的静电纺丝,并与单纯聚乙烯醇水溶液的静电纺丝进行了对比。利用扫描电镜观察纤维的形态、直径变化。结果表明:聚乙烯醇水溶液中加入少量氯化钠,由于离子的作用可以使喷射流表面电荷密度增大,静电纺丝可得到比单纯聚乙烯醇更细的纳米纤维。     

光交联PVA-SBQ/透明质酸纳米纤维的制备及性能

为了增强透明质酸的耐水溶性、实现药物缓释,本研究应用静电纺技术制备改性透明质酸(GMHA)与聚乙烯醇-苯乙烯吡啶(PVA-SBQ)的复合纳米纤维膜,进一步在紫外光照射下得到光交联复合纤维膜.系统研究了不同的紫外光照时间、温度和pH值下复合纳米纤维的溶胀比以及载药释放性能,结果表明复合纳米纤维膜的溶胀比随温度升高而减小,...     

双负载抗生素亲水性聚氨酯泡沫的制备与表征

因细菌、异物和炎症等因素引起的慢性伤口会有过量的伤口渗出液流出,影响伤口周围健康皮肤,不利于伤口愈合.针对以上问题,我们开发了双负载亲、疏水性抗生素的亲水性聚氨酯泡沫作为慢性伤口的创面敷料.通过电子显微镜观察,泡沫的孔径均匀地分布在200～400 μm之间.聚氨酯泡沫中载入的药物对聚氨酯泡沫的力学性能略有影响,对吸液率...