Preparation of albumin—PAA nanocapsules and their controlled release behavior for drugs

New kinds of narrowly distributed protein‐based nanoparticles, bovine serum albumin‐Poly (acrylic acid) (BSA/PAA) nanospheres, and nanocapsules were prepared via in situ polymerization, swelling, and re‐aggregation. The structure and morphology of the nanospheres were characterized by UV‐Vis, FT‐IR, DLS, and TEM. The stability of the BSA/PAA nanospheres and nanocapsules was increased when their skeletons were fixed by cross‐linked agents. The nanospheres carried a positive charge and their size was about 80–110 nm. The protein‐based nanocapsules were stimuli‐responsive with pH value and their hydrodynamic diameter varied from 70 to 230 nm with changes of pH. In vitro release experiments of Rhodamine B and Doxorubicin hydrochloride showed that these biopolymer nanoparticles provided a controlled release of the entrapped drugs for 300 hr. Copyright © 2009 John Wiley & Sons, Ltd.     

One-pot synthesis and characterization of crosslinked polyphosphazene dopamine microspheres for controlled drug delivery applications

Inorganic–organic hybrid and highly cross-linked poly(cyclotriphosphazene-co-dopamine) microspheres (PCTD) were successfully synthesized by a one-step precipitation polymerization technique. In the polymerization reaction, dopamine (a neurotransmitter), hexachlorocyclotriphosphazene (HCCP, N₃P₃Cl₆) and triethylamine (TEA) were used as a monomer, a crosslinker molecule and an acid acceptor, respectively. The characterization of PCTD microspheres was performed by SEM-EDX, FTIR, XRD, TGA and DLS. The particle size of microspheres were determined as 1.042?µm. The usability of synthesized novel polyphosphazene microspheres for controlled drug release was investigated using acriflavine as a model drug. Acriflavine has antimicrobial and anticancer properties. As drug release medium pH:7.4 (PBS) and pH: 5.0 buffer solutions were used. They were the pH of blood and the approximate pH of the environment in which the cancerous cells are located, respectively. PCTD microspheres have 19.5?mgg^?1 drug storage capacity and 29% (pH: 5.0) and 47% (pH: 7.4) of the acriflavine was released from PCTD microspheres at 37?°C during 7?days.     

Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug

Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.     

Photopolymerization of alicyclic methacrylate hydrogels for controlled release

Alicyclic hydroxy methacrylate monomer, o‐hydroxycyclohexyl methacrylate (HCMA), was synthesized and characterized by Fourier transformed infrared spectroscopy (FT‐IR) and proton nuclear magnetic resonance spectroscopy (¹H‐NMR). Photopolymerization kinetics of HCMA was investigated via real‐time infrared spectroscopy (RT‐IR). Polymeric network hydrogels based on hydroxyethyl methacrylate (HEMA) and HCMA were prepared by using the photopolymerization technique. Mechanical strength, swelling characteristic, and controlled release behavior of hydrogels with various feed compositions were studied. Poly(HEMA‐co‐HCMA) hydrogel had higher storage modulus than that of poly(HEMA) hydrogel as investigated by dynamic mechanical analysis (DMA). Acid orange 8 was used as a model drug for the investigation of drug release behavior of copolymeric hydrogels. Results indicated that increase in HCMA ratio in hydrogel composition could reduce the swelling rate and prolong the release time. Scanning electron microscopy (SEM) was also utilized to study the surface morphology of hydrogels, and the results indicated that HCMA content influenced pore diameter on the hydrogel surface. Copyright © 2008 John Wiley & Sons, Ltd.     

Retracted: Control of Nanoparticle Release by Membrane Composition for Dual-Responsive Nanocapsules

Stimulus-responsive polymeric nanocapsules usable as cell mimics can be engineered to precisely control cargo release. This work reports the release behavior of post-loaded nanoparticles through permeable membranes of stable pH and temperature dual-responsive polymeric nanocapsules (CP1, CP2, and CP3) with the same membrane thickness but different membrane composition, prepared by layer-by-layer assembly and surface-initiated single electron transfer living radical polymerization, respectively. These nanocapsules differ in their tunable membrane permeability for post-loaded nanoparticles as protein mimics, tailored by pH and temperature stimuli. Release mechanisms are dominated by membrane composition, such as polyelectrolyte multilayer membrane for CP1, pure cationic membrane for CP2, and valve-like functions for CP3. Thus, one can postulate the main locations of post-loaded protein mimics in the different nanocapsules. Understanding the post-loading and diffusion mechanism of nanoparticles through permeable membranes in cell mimics paves the way for the construction of new “smart” synthetic protocells with control over the exchange of bioactive nanoparticles between different compartments.     

Chemical synthesis of MnFe2O4/chitosan nanocomposites for controlled release of ofloxacin drug

In this study, we synthesized ofloxacin‐loaded MnFe₂O₄ nanoparticles (NPs) surface modified with chitosan (CS‐MnFe₂O₄) for prolonged antibiotic release in a controlled manner. It was found that the synthesized CS‐MnFe₂O₄ was spherical in shape with an average size of 30–50 nm, low aggregation, and good magnetic responsibility. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 86% of drug load and can release ofloxacin over a sustained period of 3 days. The release kinetics study reveals that the drug follows zero order kinetics and the mechanism of drug release is diffusion‐controlled type. These results indicated that CS‐MnFe₂O₄ NPs with pH‐sensitive properties can be used as candidates for intestinal targeted drug delivery through oral administration by avoiding the drug release in the highly acidic gastric fluid region of the stomach.     

Carbohydrate polymers as controlled release devices for pesticides

Controlled release technology addresses problems associated with excessive use of toxic agricultural chemicals. This paper reviews the studies on the use of carbohydrate polymers as controlled release matrices for pesticides. Alginates, starch and its derivatives, chitosan, carboxymethylcellulose and ethylcellulose are some of the natural polymers discussed in this review. The advantages and disadvantages of these polymeric systems as well as the factors that affect pesticide release are presented. A discussion on the polymers’ encapsulation efficiency and release profile is also included, which will aid future researchers in identifying the suitable formulation for controlled release of pesticides. Combination of two polymers, incorporation of sorbents into polymer matrices, and modification of polymer systems are some of the strategies also discussed herein. Recent trends in this area of research include nanoformulation, nanoencapsulation, and the development of polymeric systems with dual properties such as controlled release with photo-protective property and the attract-and-kill strategy. Cytotoxicity studies are being conducted to address safety issues of pesticide handlers as well as to determine the toxicity of the formulation to non-target organisms such as the plant itself.     

Dual crosslinked pH‐ and temperature‐sensitive hydrogel beads for intestine‐targeted controlled release

Novel drug‐loaded hydrogel beads for intestine‐targeted controlled release were developed by using pH‐ and temperature‐sensitive carboxymethyl chitosan‐graft‐poly(N,N‐diethylacrylamide) (CMCTS‐g‐PDEA) hydrogel as carriers and vitamin B₂ (VB₂) as a model drug. The hydrogel beads were prepared based on Ca²⁺ ionic crosslinking in acidic solution and formed dual crosslinked network structure. The structure of hydrogel and morphology of drug‐loaded beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The study about swelling characteristics of hydrogel beads indicated that the beads had obvious pH‐ and temperature‐sensitivity. In vitro release studies of drug‐loaded beads were carried out in pH 1.2 HCl buffer solution and pH 7.4 phosphate buffer solution at 37°C, respectively. The results indicated that the dual crosslinked method could effectively control the drug release rate under gastrointestinal tract (GIT) conditions, which was superior to traditional single crosslinked beads. In addition, the effects of grafting percentage, pH value, and temperature on the release behavior of the VB₂ were investigated. The drug release mechanism of CMCTS‐g‐PDEA drug‐loaded beads was analyzed by Peppa's potential equation. According to this study, the dual crosslinked hydrogel beads based on CMCTS‐g‐PDEA could serve as suitable candidate for drug site‐specific carrier in intestine. Copyright © 2009 John Wiley & Sons, Ltd.     

Sponge-like nanostructured conducting polymers for electrically controlled drug release

An electrically controlled drug release (ECDR) system based on sponge-like nanostructured conducting polymer (CP) polypyrrole (PPy) film was developed. The nanostructured PPy film was composed of template-synthesized nanoporous PPy covered with a thin protective PPy layer. The proposed controlled release system can load drug molecules in the polymer backbones and inside the nanoholes respectively. Electrical stimulation can release drugs from both the polymer backbones and the nanoholes, which significantly improves the drug load and release efficiency. Furthermore, with one drug incorporated in the polymer backbone during electrochemical polymerization, the nanoholes inside the polymer can act as containers to store a different drug, and simultaneous electrically triggered release of different drugs can be realized with this system.     

Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior

Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).     

甲壳胺药膜的控制释放研究

以阿司匹林为模型药物研究了小分子药物在甲壳腹膜中的释放行为，结果表明释放是扩散控制的，与膜厚、介质pH值，膜交联度及膜分散性密切相关。改变这些参数可达到比较恒定的延长释放和不同的给药途径。     

Development of temperature-responsive semi-IPN hydrogels from PVA-PNVC-PAm for controlled release of anti-cancer agent

A series of semi-interpenetrating polymeric network (semi-IPN) hydrogels were synthesized using poly(vinyl alcohol) (PVA), monomers N-vinylcaprolactam (NVC) acrylamide (Am), and cross-linker bis[2-methacryloyloxy] ethyl phosphate (BMEP). The hydrogels were synthesized by using free-radical polymerization using ammonium persulphate (APS) as an initiator at 60°C. The hydrogels were characterized by various techniques such as Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to confirm the formation, crystallinity, and morphological behavior. The swelling behavior at various temperatures and pH conditions showed that the semi-IPN hydrogels were good candidates for temperature-responsive nature. 5-Flurouracil (FU), a model anticancer drug, was successfully encapsulated and the encapsulation efficiency was found in range of 50–74% for different hydrogels. Further, in-vitro release studies were performed to investigate the release mechanism. The cumulative release studies showed that the developed hydrogels are potentially efficient for the gastrointestinal drug delivery of FU.     

Novel drug delivery system of hollow mesoporous silica nanocapsules with thin shells: preparation and fluorescein isothiocyanate (FITC) release kinetics

Core-shell nanoparticles of Au@silica with a diameter of approximate 45–60 nm and wall thickness in range of 3–10 nm were synthesized by using 40 and 50 nm gold nanoparticles as the templates. The mesoporous particles are regulated by 3-aminopropyltrimethoxysilane addition. Hollow mesoporous silica nanocapsules (HMSNs) were prepared by using sodium cyanide to dissolve the gold cores. The characterization of Au@silica and HMSNs by transmission electronic microscope indicated that the silica shells were uniform and smooth, and also the porosity was proved by fluorescein isothiocyanate (FITC) release experiments. The ratio of hollow core to HMSNs is more than 70%. HMSNs were subsequently used as drug carrier to investigate FITC (as a model drug) release behaviors in vitro. Fluorescent spectrometry was performed to determine the release kinetics from the HMSNs. The release profiles are significantly different as compared with the control (free FITC), which show that HMSNs are good drug carriers to control drug release, and have high potential in therapeutic drugs delivery in future applications.     

Micelle-like macromolecular systems for controlled release of daunomycin

Soluble macromolecular conjugates for the delivery of the strongly hydrophobic anticancer drug daunomycin (DM) or rubomycin with its controlled release were prepared. The solution properties of these conjugates consisting of DM bonded to copolymer of maleic anhydride and divinyl ether (DIVEMA) and a few model compounds were investigated using adsorbance spectroscopy, as well as surface activity and solubilization of water-insoluble dye measurements. The data of these studies indicated that in water solutions conjugates are associated, probably intramolecularly. This micellization in parallel with an H-bonded ionic complex between DM and polymer carrier determines the DM release. It is concluded that the desirable drug release can be achieved through changing the structure of conjugates by means of varying the constituents hydrophobicity. © 1998 John Wiley & Sons, Ltd.     

Biodegradable polymer/clay systems for highly controlled release of NPK fertilizer

The aim of this work was to obtain biodegradable polymeric systems based on poly(hydroxybutyrate) (PHB) for use in the controlled release of agrochemicals and to analyze the relationship between the properties of polymers and the rates of release of active compounds. Two types of systems were obtained: one using nitrogen, phosphorous, and potassium (NPK) fertilizer directly mixed within the polymer matrix and another with the fertilizer previously incorporated in bentonite (Bent) and mixed with the polymer. The systems were obtained by melt processing and then evaluated by their properties. The release of the active compounds was analyzed by conductometric analysis using an aqueous solution as release medium for 240 hours. The obtained results were correlated with the biodegradation process of PHB. All of the systems presented a significant reduction in the active compounds released to the environment as compared with the direct application of NPK. The PHB/NPK systems showed a release of up to 37% of the compounds, while the PHB/m‐Bent showed greater control, with a release between 4% and 11% after 240 hours. In addition, the properties of the polymer systems presented a direct relationship with the rate of active compounds released. The type of production process, properties, and biodegradability indicate interesting potential of these systems for application in the controlled release of active compounds.     

壳聚糖纳米微球对牛血清蛋白的包封和缓释效果研究

壳聚糖(chitosan,CS)是甲壳素脱乙酰化的产物,是由葡萄糖结构单元组成的直链多糖。CS作为一种带正电荷的天然多糖,本身具有无毒、无刺激性、无致敏性、无致突变的性质,降解产物为低分子壳寡糖和葡萄糖胺,具有良好的生物相容性和生物降解性[1-2]。CS本身具有的特性,引起了人们的     

Preparation, characterization, and controlled release of novel nanoparticles based on MMA/beta-CD copolymers

A series of random copolymers with different beta-cyclodextrin contents were synthesized by radical copolymerization of MMA with a monovinyl beta-CD monomer. The copolymers were characterized with IR spectroscopy, elemental analysis, DSC, and TGA. Based on these copolymers, their nanoparticles were prepared by using DMF, water, and acetone as solvents. Aqueous dispersions of the nanoparticles were further obtained by dialysis against water. Zetasizer Nano-ZS dynamic light scattering and transmission electron microscopy were employed to characterize the nanoparticles. Using camptothecin as a model drug molecule, the encapsulation efficiency and release behavior of the nanoparticles were investigated.     

Stimuli-responsive chitosan-graft-poly(N-vinylcaprolactam) as a promising material for controlled hydrophobic drug delivery

A novel type of pH- and thermo-responsive copolymer, chitosan-graft-poly(N-vinylcaprolactam) (chitosan-g-PNVCL), was prepared by grafting carboxyl-terminated poly(N-vinylcaprolactam) (PNVCL-COOH) chains onto a chitosan backbone as a drug-delivery carrier. The formation of chitosan-g-PNVCL was confirmed by FT-IR and 1H NMR techniques. Chitosan-g-PNVCL showed a definite phase transition at 32 degrees C as occurs in pure PNVCL. The swelling degree of the chitosan-g-PNVCL beads was found to be higher at pH 2.2 than at pH 7.4. Moreover, the swelling degree of the beads decreased with increased environmental temperature. Compared to the chitosan beads, the release profile of chitosan-g-PNVCL beads showed a slower and more controlled release of the entrapped ketoprofen. The release behavior of the chitosan-g-PNVCL beads was influenced by both the pH and temperature of the medium. The MTT assay showed no obvious cytotoxicity of chitosan-g-PNVCL against a human endothelial cell line over a concentration range of 0-400 microg x mL(-1). These results suggest that chitosan-g-PNVCL could be a potential stimuli-responsive material for controlled drug delivery, and it may improve the bioavailability, efficacy, and compliance of the encapsulated drugs. [Reaction: see text].     

Multiphase thermoplastic hybrid for controlled release of antimicrobial essential oils in active packaging film

Active packaging, a new technology concept in the field of food packaging, has been introduced in recent years in order to provide quality and safety, as well as extend the shelf life of food products. Antimicrobial (AM) agents can be incorporated directly into the active packaging and migrate in a controlled manner to the headspace between the food and the package, inhibiting bacteria growth on the food surface. Naturally derived AM agent, such as essential oils (EOs), has received considerable attention for food preservation purposes, because of their effective AM activity against various bacteria and fungi. In the present study, AM active film systems based on polypropylene/polyamide blends, montmorillonite nanoclays, and thymol EO were produced to investigate the feasibility of controlling the release rate of thymol from food packaging systems. Selective localization of thymol in a specific phase in the system that derives from thermodynamic affinity was assumed to be useful in controlling its migration rate from the film to the headspace. EO retention in the film under two different time conditions was measured by spectroscopic analysis. The release rate of EO was determined using Gas chromatography technique and analyzed by diffusion model approach. Inhibition of bacterial growth was periodically tested for Listeria and Escherichia coli bacteria. This study confirms the thermodynamic affinity of polyamide phase with thymol that has a positive effect in retaining the EO. Results show controlled AM behavior of the active packaging films, based on various blend compositions. Copyright © 2016 John Wiley & Sons, Ltd.     

Polymeric controlled release formulations of niclosamide for control of Biomphalaria alexandrina, the vector snail of schistosomiasis

Schistosomiasis is one of the most important public health problems in many developing countries. The present study was conducted to investigate the effect of the polymeric niclosamide formulations against Biomphalaria alexandrina snails, the intermediate host of Schistosoma mansoni in Egypt. Three new polymeric formulations were prepared for the molluscicide niclosamide. The formulations were prepared either by the chemical modifications of poly(glycidyl methacrylate) or by physical entrapment of the niclosamide in calcium alginate beads. The release of the niclosamide from the polymeric formulations was investigated. The activity of the prepared formulations against Biomphalaria alexandrina was investigated. The results obtained revealed higher potency for polymerized niclosamide B3 than B1; the lowest potency was revealed for B2. After an exposure period of 24 hours, LC(50) values were 0.073, 0.098 and 1.09 ppm for B3, B1 and B2, respectively. In addition, the molluscicidal potency of the test polymeric niclosamide was age-dependent, where old snails were more tolerant to the test solutions than young and newly hatched snails. The results also indicated that the molluscicidal activity of B3 was extended for 21 days and 17 days for B1, compared with 5 days for free niclosamide. However, the molluscicidal potency of the polymerized niclosamide was increased after boiling for one hour, and was increased with increasing the pH of the medium to pH 9. In addition, their potency was increased with decreasing the water hardness concentrations (CaCO(3)).Molluscicidal activity of free niclosamide and its polymeric formulations vs. exposure time.