Sustained release drug delivery using supramolecular hydrogels of the triblock copolymer PCL–PEG–PCL and α-cyclodextrin

Supramolecular hydrogels (SMGel) have attracted much attention as a drug and gene delivery system in recent years. In this study, SMGels based on the tri-block copolymer of poly-ε-caprolactone–polyethylene glycol–poly-ε-caprolactone (PCL–PEG–PCL) and α-cyclodextrin (α-CD) were prepared and evaluated for the delivery of two model drugs, naltrexone hydrochloride and vitamin B₁₂. Tri-block copolymers were synthesized easily in 15 min by ring-opening polymerization using the microwave irradiation technique, and their structures were determined by gel permeation chromatography and nuclear magnetic resonance methods. SMGels composed of various concentrations of the copolymer and α-CD were prepared and characterized for their rheological behaviour, their gel formation time and in vitro drug release profile. The results indicated that copolymers with a PCL to PEG ratio of 1:4 are suitable for SMGel preparation. The most viscose system with good syringeability was prepared by mixing 12 % wt α-CD and 10 % wt of copolymer. The gelation was found to occur within a minute after mixing. The viscosity of the hydrogel systems was determined as a function of shear rate. Finally, in vitro B₁₂ release through the hydrogel systems was studied. Up to 80 % of Vitamin B₁₂ was released through this system during a period of 20 days. Rheological evaluation revealed that the hydrogel has shear thinning properties, and the system regained its ground rheological state in a time dependent manner. Polymer concentration did not affect the drug release profiles. Finally, it was concluded that such systems are appropriate drug delivery systems due to their ability to provide a controlled drug release profile and their shear thinning thixotropic behaviour, which makes them syringeable and injectable.     

Light-triggered reversible assemblies of azobenzene-containing amphiphilic copolymer with β-cyclodextrin-modified hollow mesoporous silica nanoparticles for controlled drug release

Hollow mesoporous silica nanoparticles (HMSs) were modified by β-cyclodextrin via a "click" reaction, an amphiphilic copolymer with a trans-azobenzene structure was then assembled onto β-cyclodextrin to cover the surface of the HMSs. The prepared nanocomposites can release drugs in a "release-stop-release" manner by converting light irradiation.     

Core–shell nanoparticles of carboxy methyl cellulose and compritol-PEG for antiretroviral drug delivery

Multi-functional nanoparticles hold great promise for the effective treatment of many diseases. Zidovudine a commonly used anti-HIV drug, requires a delivery system for more effective treatment of AIDS. The present study focuses on the development of anti-viral drug-loaded hybrid nanoparticles (LPNs) of lipid and polymer consisting of carboxy methyl cellulose—zidovudine (AZT) core enclosed by a compritol (Comp)-polyethylene glycol shell. The characterization of drug loaded LPNs was done using TEM, DLS and FT-IR analysis. The drug loading efficiency, drug release, blood compatibility, MTT assay and cell uptake studies were carried out using the LPNs. The synthesized nanoparticles exhibited core–shell morphology with an average size of 161.65 ± 44.06 nm; the LPN also demonstrated 82% drug encapsulation efficiency with slow drug release behaviour. The hybrid nanoparticles were found to be blood compatible and non toxic. The rhodamine-labeled hybrid nanoparticles were also found to effectively enter the brain cells. The novel hybrid drug delivery system shows controlled drug release, biocompatibility and high drug loading efficiency. These LPNs obtained from natural polymers can provide an excellent platform for designing systems for targeted drug delivery.     

Investigation of controlled release properties and anticancer effect of folic acid conjugated magnetic core–shell nanoparticles as a dual responsive drug delivery system on A-549 and A-431 cancer cell lines

Research on Chemical Intermediates - Epirubicin loaded on magnetite-coated calcium ferrite conjugated folic acid (Fe3O4@CaFe2O4-FA@EPI) was synthesized and characterized using various techniques...     

Nanoparticle carriers based on copolymers of poly(ε-caprolactone) and hyperbranched polymers for drug delivery

Novel amphiphilic copolymers based on poly(ε-caprolactone) (PCL) and hyperbranched poly (amine-ester) (HPAE) with various compositions were synthesized. The amphiphilic copolymers can self-assemble into nanoscopic micelles and their hydrophobic cores can encapsulate doxorubicin (DOX) in aqueous solutions. The DOX-loaded HPAE-co-PCL nanoparticles diameter increased from 121 to 184 nm with the increasing PCL segment in the copolymer composition. An in vitro study at 37°C demonstrated that DOX-release from nanoparticles at pH 5.0 was much faster than that at pH 7.4. The cytotoxicity for HeLa cells study demonstrated that DOX-loaded HPAE-co-PCL nanoparticles exhibited the anti-tumor effect was enhanced significantly, suggesting that the DOX-loaded HPAE-co-PCL nanoparticles have great potential as a tumor drug carrier.     

Effect of epoxidized palm oil on the mechanical and morphological properties of a PLA–PCL blend

In this study, the effects of epoxidized palm oil (EPO) on the mechanical and morphological properties of a blend of two types of biodegradable polymer, poly(lactic acid) (PLA) and polycaprolactone (PCL), were investigated. The solution-casting process, with chloroform as a solvent, was used to prepare samples. Addition of EPO reduced the tensile strength and modulus but increased elongation at break for the PLA–PCL blend. The highest elongation at break was observed for the blend with 10 % (w/w) EPO content. Scanning electron microscopy (SEM) indicated that the fractured surface morphology of the PLA–PCL blend became more stretched and homogeneous in PLA–PCL–EPO. Possible interactions between the PLA–PCL blend and EPO were also characterized by use of Fourier-transform infrared (FTIR) spectroscopy. Thermal stability was studied by differential scanning calorimetry and thermogravimetric analysis. The results from FTIR and SEM revealed that the miscibility of the PLA–PCL blend was improved by addition of EPO.     

Investigating the effect of PEG200 and two-dimensional h-BN on PVDF membrane performance for membrane distillation–crystallization

Although water supplies are prominently dependent on desalination technology, desalination plant facing severe issues of discharged brine concentrate. Membrane distillation crystallization is an emerging synergistic technology that resolves the issue of brine concentrate by recovering clean water and value-added minerals simultaneously. In the present study, properties of polyvinylidene fluoride (PVDF) membrane were modified by incorporation of exfoliated fillers of hexagonal boron nitride and polyethylene glycol. The changes in morphology, surface roughness, hydrophobicity, thermal stability, and chemical composition of the prepared membranes were evaluated by scanning electron microscopy, atomic force microscopy, contact angle, thermogravimetric analysis, Fourier-transform infrared spectroscopy, respectively. Membrane distillation crystallization experiments were conducted to observe the effect of modified membranes on the permeate flux and salts recovery at different feed temperatures. The results showed a significant improvement in the permeate flux with modified membranes compared with pure PVDF membrane. It was found that hexagonal boron nitride/polyethylene glycol200 incorporated PVDF membrane gave the higher permeate flux (3.41 kg/m² h for K₂SO₄ and 2.62 kg/m² h for KNO₃) at a temperature of 80 °C along with higher salts recovery than pure PVDF membranes. A 100 h long run test was conducted on modified membranes, which showed consistency in permeate flux with a marginal increase in conductivity.     

Biomimetic approach towards the preparation of hydroxyapatite and hydroxyapatite/chitosan/β-cyclodextrin nanoparticles: application to controlled drug release

Hydroxyapatite (HAp) and hydroxyapatite/chitosan/β-cyclodextrin (HAp/CS/β-CD) nanoparticles were successfully prepared in the modified simulated body fluid (SBF) solution at the physiological conditions (pH 7.4, temperature?=?37 °C). CS/β-CD nanoparticles acted as templates for the synthesis of HAp/CS/β-CD nanoparticles to improve the nanoarchitecture of HAp and its crystallinity.The nanoparticles were characterized by FT-IR spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Kneading and coprecipitation methods were applied to prepare the inclusion complex involving β-CD and p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin), a photosensitizer for anti-cancer drugs. The 1:1 stoichiometric ratio of the formed inclusion complex was characterized by a formation constant of 7.216?×?10² mol^?1 dm³ and analyzed by ¹H NMR, FTIR, and UV–Vis. The p-THPP delivery release in vitro was in this order: HAp/CS/β-CD?<?CS/β-CD?<?<?HAp/β-CD?<?β-CD, hinting at a better controlled release by HAp/CS/β-CD nanoparticles.     

Biodegradable and thermoresponsive micelles of triblock copolymers based on 2-(N,N-dimethylamino)ethyl methacrylate and ε-caprolactone for controlled drug delivery

Amphiphilic triblock copolymers, poly(2-(N,N-dimethylamino)ethyl methacrylate)_x-block-poly(caprolactone)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate)_x, PDMAEMA_Co, were synthesized. Polymerization and structural features of the polymers were analyzed by different physicochemical techniques (GPC, ¹H NMR and FTIR). Formation of hydrophobic domains as cores of the micelles was studied by ¹H NMR and further confirmed by fluorescence. Dynamic light scattering measurements showed a monodispersed size distribution only for the copolymer with the lowest degree of polymerization, while increasing the length of PDMAEMA blocks leads to a bimodal size distribution. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PDMAEMA at temperatures between 54 and 87 °C. The triblock copolymer micelles were loaded with the sparingly water-soluble anticancer drug, chlorambucil, by a dialysis procedure. The drug release profile monitored by fluorescence showed that the release of chlorambucil from PDMAEMA nanoparticles is controlled by a combined degradation-diffusion mechanism.     

Core–shell thermal-responsive and magnetic molecularly imprinted polymers based on mag-yeast for selective adsorption and controlled release of tetracycline

A novel thermal-responsive and magnetic molecularly imprinted polymers (TMMIPs) were prepared based on mag-yeast via a mild and effective method; the obtained TMMIPs were used for selective adsorption and release of tetracycline from aqueous solution. Imprinted polymerization directly occured on the surface of microspheres, and core–shell imprinted polymers were developed via in situ precipitation polymerization. The properties of obtained TMMIPs were characterized by scanning electron and transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectra, thermo-gravimetric analysis and so on. The adsorption equilibrium data were well described by Langmuir isotherm model. Kinetic experiments showed the adsorption process reached the equilibrium within 60 min, and the pseudo-second-order kinetic model was used to fit the adsorption data well. TMMIPs exhibited magnetic sensitivity, magnetic stability and thermal stability. Reversible recognition and release of template molecule were realized by changing environmental temperatures. Several other antibiotics were selected as model analytes to evaluate the selective recognition performance of TMMIPs. The TMMIPs have good temperature response, selectivity and reusability, making them possible in applying for antibiotics adsorption and controlled release.     

The effect of framework functionality on the catalytic activation of supported Pd nanoparticles in the Mizoroki–Heck coupling reaction

Palladium nanoparticles (Pd-NPs) were supported on functional and nonfunctional Co-coordination polymers (Pd/CoBDCNH₂ and Pd/CoBDC). Advanced analytical techniques revealed that Pd-NPs are supported on the external surface of the polymer framework and the functionalized framework possesses effective influence to prevent Pd-NP aggregation. Supported Pd-NPs were effectively applied as heterogeneous recyclable catalysts in the Mizoroki–Heck C–C cross coupling reactions of iodobenzene and either aromatic or aliphatic terminal alkenes. Catalytic results exhibited that highly dispersed Pd-NPs with low loading (1%) on the functional polymer (Pd/CoBDCNH₂) are more effective than aggregated Pd-NPs with high loading (9%) on the nonfunctional polymer (Pd/CoBDC). Both catalysts can simultaneously provide high activity and selectivity to E-coupled products, high efficiency in low amounts, easy separation of heterogeneous catalyst and appropriate performance in the recycling reaction without addition of a reducing agent.     

Behavior of nonionic emulsifier molecules on the preparation of nanoparticles from submicron-sized ionized styrene–methacrylic acid copolymer particles by the particle dissolution method

 Submicron-sized styrene–methacrylic acid copolymer (92/8 molar ratio) particles dissolved in the presence of polyoxyethylene nonylphenylether nonionic emulsifier under alkaline conditions at 90 °C, resulting in nanoparticles with diameters of about 30 nm. In order to clarify the role of the emulsifier molecules in the dissolution process, ¹H NMR measurements were carried out. As the particles swelled, the NMR integrals due to the emulsifier decreased markedly. This indicates that the emulsifier molecules permeated into the inside of the alkali-swelling particles and were adsorbed on the polymer molecules, which supports the formation mechanism of nanoparticles by the particle dissolution method proposed in a previous article. Received: 10 December 1998 Accepted in revised form: 1 April 1999     

Anti-allergic effect of the flavonoid myricitrin from Myrica rubra leaf extracts in vitro and in vivo

Flavonoids are ingested by the general population as anti-oxidant and anti-inflammatory agents. In this study, we investigated the effects of myricitrin, a flavonoid rich in Myrica rubra leaf, upon anti-inflammatory action. Myrica rubra leaf extracts inhibited pro-inflammatory TNFα production in a macrophage cell line, Raw264.7 cells. We observed that the serum IgE levels in the leaf extract-treated DO11.10, a mouse allergy model, were down-regulated. HPLC was performed to demonstrate that M. rubra leaf extracts contain a large amount of myricitrin. We observed an inhibitory effect of HPLC-purified myricitrin on TNFα production in Raw264.7 cells. Thus, myricitrin may be of potential interest in the management of inflammatory conditions.     

Simultaneous release of hydrophobic and cationic solutes from thin-film "plum-pudding" gels: a multifunctional platform for surface drug delivery?

The release of two compositionally different solutes from a composite gel composed of two different populations of microgel particles embedded in a single bulk gel matrix is described, showing the potential of the "plum-pudding gel" as a multifunctional platform for controlled surface release. One hydrophobic solute (pyrene) and one hydrophobic and charged solute (rhodamine 123) were chosen as the solutes to be released. Hydrophobic microgels composed of 50% N-isopropylacrylamide (NIPAM) and 50% N-tert-butylacrylamide (BAM) were loaded with pyrene, and anionic microgels composed of 30% acrylic acid (AAc), 20% NIPAM, and 50% BAM were loaded with rhodamine 123. The two solute-loaded microgel populations were incorporated into a single bulk gel network, from which the two solutes were released simultaneously and independently. Using this structural motif, solutes that are mutually incompatible can be incorporated into a single matrix with which they may also be incompatible. The electrostatically incorporated solute was released much more slowly than the hydrophobically attracted solute, indicating that the microgel composition can be tailored to the specific solute, and thus control its release rate. The choice of bulk matrix was also found to influence the release rate much more than expected, offering a further control element to the system.     

Fabrication,controlled release,and kinetic studies of indomethacin—layered zinc hydroxide nanohybrid and its effect on the viability of HFFF2

The intercalation of indomethacin into the interlayer gallery of layered zinc hydroxide (LZH) has been successfully executed using the simple ion exchange approaches. The synthesized intercalation compound, indomethacin-LZH nanohybrid, was characterized using PXRD, FTIR, SEM, BET, and STA. From the PXRD results, the intercalation of indomethacin anions into the interlayer gallery of LZH was successful; showing the formation of a new peak at lower 2θ with a basal spacing of 21.96?Å. FTIR analysis of the nanohybrid further supported the presence of indomethacin in the interlayer of the indomethacin-LZH nanohybrid. STA analysis confirms that the nanohybrid has higher thermal stability than pure indomethacin. The in vitro release mechanism of the indomethacin anions from the indomethacin-LZH nanohybrid showed slow release, with 95% and 78% release in phosphate buffer saline (PBS) solution at pH 4.8 and 7.4, respectively. The release behavior of indomethacin from its intercalation compounds in PBS solution at pH 4.8 and 7.4 follows the Higuchi model. In addition, the nanohybrid treated with normal fibroblast cell line shows that it reduces cell viability in a dose and time-dependent manner. This study shows that the high potential of the nanohybrid as an encapsulated material for the controlled release formulation of nonsteroidal anti-inflammatory (NASID) anions.     

Novel potentiometric immunosensor for determination of diphtheria antigen based on compound nanoparticles and bilayer two-dimensional sol–gel as matrices

A novel method for fabrication of a diphtheria potentiometric immunosensor has been developed by means of self-assembling compound nanoparticles to a thiol-containing sol–gel network. A cleaned gold electrode was first immersed in a 3-mercaptopropyltrimethoxysilane (MPS) sol–gel solution to assemble a silica sol–gel monolayer. The silane entities were then polymerized into a two-dimensional sol–gel network (2D network) by dipping into aqueous NaOH. The second silane layer was formed by re-immersion in the MPS sol–gel solution overnight. The compound nanoparticles (nanocompounds) containing gold nanoparticles and silver nanoparticles were then chemisorbed on to the thiol groups of the second silane layer. Finally, diphtheria antibody (anti-Diph) was adsorbed on to the surface of the compound nanoparticles. The modified process was characterized by cyclic voltammetry (CV). Detection is based on the change in the potentiometric response before and after the antigen–antibody reaction. A direct potentiometric response to diphtheria antigen (Diph) was obtained from the immobilized diphtheria antibody. The potentiometric response of the resulting immunosensor was rapid and the linear range was from 22 to 800 ng mL^–1 with the linear regression equation E=–79.5+69.4 log [Diph] and a detection limit of 3.7 ng mL^–1 (at 3). Up to 19 successive assay cycles with retention of sensitivity were achieved for probes regenerated with 0.2 mol L^–1 glycine–hydrochloric acid (Gly–HCl) buffer solution. Moreover, analytical results from several serum samples obtained using the developed technique were in satisfactory agreement with those given by the ELISA method, implying a promising alternative approach for detecting diphtheria antigen in clinical diagnosis.     

Effect of block lengths on the association behavior of poly(l-lactic acid)/poly(ethylene glycol) (PLA–PEG–PLA) micelles in aqueous solution

A series of poly(l-lactic acid)/poly(ethylene glycol) triblock copolymers with a PLA–PEG–PLA architecture were synthesized by a ring-opening polymerization (ROP) process. The copolymers were characterized by ¹H NMR and GPC. The total number average molecular weights were in the range of 4,700–50,000, whereas the degrees of polymerization of the PLA and PEG blocks varied from 15 to 359 and from 68 to 136, respectively. The self-association of these copolymers in aqueous environment was studied by emission fluorescence spectroscopy of anilinonaphthalene probe and the critical association concentration (CAC) of the copolymers was measured. It was found that the micellization process of these copolymers was mainly determined by the length of the hydrophobic LA block, while the length of the hydrophilic PEG block had little effect. Furthermore, the low CAC values of the copolymers suggest that the copolymers form stable supramolecular structures in aqueous solutions.     

Electrochemical synthesis of copper nanoparticles on nafion–graphene nanoribbons and its application for the synthesis of diaryl ethers

Electrochemical synthesis of copper nanoparticles on nafion–graphene nanoribbons support for the synthesis of diaryl ethers via Ullmann type coupling is reported. The catalyst showed excellent performance for C–O cross coupling reactions under ligand free condition. The catalyst was characterized by various techniques such as SEM, TEM, XRD, EDX, BET, TGA, and UV spectrophotometry. It was recycled several times without significant loss in its catalytic activity.