Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery

Many synthetic polycationic vectors for non-viral gene delivery show high efficiency in vitro, but their usually excessive charge density makes them toxic for in vivo applications. Here we describe the synthesis of a series of high molecular weight terpolymers with low charge density, and show that they exhibit efficient gene delivery, some surpassing the efficiency of the commercial transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl diester and amino diol, and their hydrophobicity adjusted by varying the lactone content and by selecting a lactone comonomer of specific ring size. Targeted delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the terpolymers results in significant inhibition of tumour growth, with minimal toxicity both in vitro and in vivo. Our findings suggest that the gene delivery ability of the terpolymers stems from their high molecular weight and increased hydrophobicity, which compensates for their low charge density.     

Investigation of swellable poly (N-isopropylacrylamide) based hydrogels for drug delivery

The thermo-sensitive properties of poly (N-isopropylacrylamide) (PNIPA) hydrogels are modified by the addition of hydrophilic acrylamide comonomers and an interpenetrating network of sodium alginate for drug delivery applications near 37 °C. A mathematical model is presented to describe the mass transport kinetics during the hydrogel drug delivery process, which is accompanied by a volume change during phase transition. In this model, the transport in the polymer matrix is described by Fick's second law in cylindrical coordinates, with concentration dependent diffusion coefficients. The moving boundary problems caused by the polymer matrix swelling are also solved by numerical simulation. The models show that the Trypan blue release from the modified PNIPA-based hydrogels is strongly concentration dependent. The sodium alginate component is also shown to effectively facilitate the diffusion process. The results from the simulation are in good agreement with the measurements of diffusion and swelling observed from in vitro experiments. The implications of this work are also discussed for practical drug delivery systems.     

Temperature effects on photoluminescence of poly [2-methoxy-5-(20-ethyl-hexyloxy)-1,4-phenylene vinylene]

We present photoluminescence studies as a function of temperature from poly [2-methoxy-5-(20-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV). The photoluminescence transition energies are red-shifted with decreasing temperatures that can be explained by the suppression of the torsional motion in the polymer backbone, which increased the effective conjugation length of the polymer. The enhancement of the relative intensity of the 0–1 to 0–0 vibronic band can be attributed to the formation of aggregates in coincidence with the vibronic 0–1 bands.     

Carrier transport and luminescence properties of nanocomposites of poly[2-methoxy-5-(2-ethyl hexyloxy)-p-phenylene vinylene] and dehydrated nanotubes titanic acid

The carrier transport capability and luminescence efficiency of poly(2-methoxy-5-(2-ethyl hexyloxy)-p-phenylene vinylene) (MEH-PPV) films are enhanced by doping with dehydrated nanotubed titanic acid (DNTA). MEH-PPV molecules, either wrapped on the outer surface of or encapsulated into DNTA pores, have a more open, straighter conformation than undoped molecules, which induces a longer conjugated backbone and stronger interchain interactions, thereby, enhancing carrier mobility. MEH-PPV molecules within DNTA pores have higher exciton recombination efficiency owing to quantum confinement and the antenna effect.     

Encapsulation of curcumin within poly(amidoamine) dendrimers for delivery to cancer cells

Curcumin has anti-proliferative and pro-apototic properties against a variety of cancer cells in vitro. Unfortunately, the water-insolubility and instability leads to its low bioavailability in vivo tests. Here, we report a general approach to using poly(amidoamine) dendrimer with acetyl terminal groups to encapsulate curcumin(G₅-Ac/Cur) for drug delivery to cancer cells. The solubility, release kinetics, anticancer activity, and apoptotic-related protein expression (Bax and Bcl-2) were investigated in detail. Comparing with curcumin, the water-solubility value of G₅-Ac/Cur increased 200-fold, and the release of curcumin from the complexes was in a sustained manner. G₅-Ac/Cur showed higher anti-proliferative activity against A549 cell lines and had the better effect on the generation of intracellular reactive oxygen species, the mitochondrial membrane potential and cell apoptosis. Furthermore, the ratio of Bax/Bcl-2 was higher in samples treated with G₅-Ac/Cur. The results indicated that the G₅-Ac drug delivery system could improve the solubility and anti-cancer effect of curcumin.     

Luteinizing hormone‐releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF‐7 breast cancer cells

The purpose of this study was to design a targeted anti‐cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross‐linking method using Zn²⁺ ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE₇₂, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carboiimid HCl as cross‐linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier‐transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non‐targeted ones were studied on MCF‐7 cells which overexpress luteinizing hormone‐releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC₅₀ for MCF‐7 cells compared to free DOX and non‐targeted NPs.Inspec keywords: nanoparticles, polymer blends, cancer, cellular biophysics, drug delivery systems, drugs, biomedical materials, zinc, positive ions, Fourier transform infrared spectra, nanomedicine, proteinsOther keywords: luteinizing hormone‐releasing hormone, poly(methyl vinyl ether maleic acid), doxorubicin delivery, MCF‐7 breast cancer cell, anticancer drug delivery system, doxorubicin‐loaded PVM‐MA nanoparticle, ionic cross‐linking method, zinc ion, doxorubicin‐polymer ratio effect, zinc‐polymer ratio effect, particle size, zeta potential, loading efficiency, release efficiency, chemical coating, tiptorelin‐polyallylamin conjugation, PVM‐MA nanoparticle surface, 1‐ethyl‐3‐(3‐dimethylaminopropyl) carboiimid HCl, cross‐linking agent, Bradford assay, Fourier transform infrared spectroscopy, cytotoxicity, LHRH receptor, SKOV3 cell, Thiazolyl blue tetrazolium bromide assay, conjugation efficiency, time 72 h, Zn²⁺      

Synthesis and characterization of hydrogels based on poly(2-hydroxyethyl methacrylate) for drug delivery under UV irradiation

The present study aims to create a controlled release system through the preparation and characterization of hydrogels based on 2-hydroxyl ethyl methacrylate (HEMA). In order to investigate the influence of photo-initiators on the drug release behavior of the resulting hydrogels, three different photo-initiators [2,2-dimethoxy-2-phenyl-acetophenone] (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184) and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) were used. In addition, hydroxyapatite (HAp) was employed to modify HEMA hydrogels. The synthesis of hydrogels was confirmed by characterization through Fourier transform infrared spectroscopy, nuclear magnetic resonance (¹³C NMR) spectroscopy and digital microscope. The responsive behaviors were investigated by recording swelling ratios under different conditions. In vitro drug release studies were performed for donepezil hydrochloride-loaded hydrogels at pH 1.2, 6.8 and 7.4. The results indicated that hydrogels synthesized using Irgacure 2959 released the maximum amount of donepezil hydrochloride. Moreover, the release rate decreased in the presence of HAp.     

Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions.

Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin.

Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0?±?1.7% and 46.0?±?1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4?months at room temperature and at 4?°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution.

Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.     

Memory effect in a junction-like CdS nanocomposite/conducting polymer poly[2-methoxy-5-(2-ethylhexyloxy)1,4-phenylene-vinylene] heterostructure

The operation of a nonvolatile memory device is demonstrated using junction-like CdS nanocomposites embedded in a polymer matrix. The capacitance-voltage characteristics of Al/conducting polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-vinylene]/CdS nanocomposites in a polyvinyl alcohol matrix/indium tin oxide device exhibit hysteresis, which is attributed to the trapping, storage, and emission of holes in the quantized valence band energy levels of isolated CdS nanoneedles. The characteristics at different operating frequencies show that the hysteresis is due to trapping of charge carriers in CdS nanocomposites rather than in the interfacial states. The memory behavior in the inorganic/organic heterostructure is explained on the basis of a simple energy band diagram.     

Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines

Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.     

Photocurrent generation in a CdS nanocrystals/poly[2-methoxy-5-(2′-ethyl-exyloxy)phenylene vinylene] electrochemical cell

In this paper the photoelectrochemical processes occurring in composites formed of organic-capped CdS nanocrystals and low molecular weight poly[2-methoxy-5-(2′-ethyl-exyloxy)phenylene vinylene] conjugated polymer were investigated. High quality colloidal CdS nanoparticles were synthesized by means of thermal decomposition of suitable precursors in non coordinating solvents, using oleic acid as surface capping agent.

The absorption and emission properties of the prepared heterojunctions were studied both in solutions and in composite films.

The dispersed hybrids were also investigated as photoactive materials, focusing on the photoinduced charge transfer and recombination processes at the interface between the two components. The composites have shown a fundamental role in photoelectrochemical applications due to the presence of a great number of interfaces able to enhance the charge transfer between mixture components.

Blend solutions prepared with octylamine capped CdS nanocrystals showed an improvement of the photoconductivity with respect to hybrids containing longer oleate surfactants.     

Electroluminescence of zinc selenium (ZnSe) nanocrystals co-doped with poly[2-methoxy-5-(2'-ethylhexyloxy-p-phenylenevinylene)] (MEH-PPV)

We have synthesized water soluble zinc selenium (ZnSe) nanocrystals by using mercaotoacetic acid (TGA) as the stabilizer. The synthesized ZnSe nanocrystals were co-doped with poly[2-methoxy-5-(2'-ethylhexyloxy-p-phenylenevinylene)] (MEH-PPV) to fabricate an organic/ inorganic hybrid multilayer light-emitting device (LED). The structure of the device was indium-tin-oxide (ITO)/poly (ethylene-dioxythiophene):poly(styrenesul-fonate) (PEDOT:PSS)/MEH-PPV:ZnSe/bathocuproine (BCP)/tris-(8-hydroxylquinoline)-aluminum (Alq3)/Al. We demonstrate that the device has a lower driving voltage and increased current densities and power efficiencies owing to the co-doped ZnSe quantum dots. We obtained good efficiency of the devices when the quality ratio of MEH-PPV and ZnSe quantum dots was 1:1.     

聚[9-甲基-9-(8-硫代乙酸辛酯基)-芴]的合成及其金纳米粒子复合物

合成了一种新型的侧链含硫代乙酸辛酯基的聚芴衍生物,聚[9-甲基-9-(8-硫代乙酸辛酯基)-芴](PFMOTA).用这种聚合物修饰金纳米粒子,得到了稳定的PFMOTA/金纳米粒子复合物.采用TEM、GPC、FTIR、UV-vis和PL光谱对聚合物及其修饰的金纳米粒子复合物的结构和性能进行了表征.     

Thermal analysis of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels

The influence of water on the physical properties of a hydrogel is important for understanding natural tissues and in designing synthetic materials to replace them. In this study, poly (2-hydroxyethyl methacrylate) (pHEMA) was used as a model system to understand how water interacts with the polymer of a hydrogel. Thermal analysis methods (thermogravimetric analysis coupled to mass spectrometry and differential scanning calorimetry) were used to determine: (i) the total water content of pHEMA gels; (ii) how this water was lost during heating; (iii) the relationship between water content of the gel and its glass transition temperature; and (iv) the behavior of the water in the gel on cooling. Previous researchers have invoked various models to describe the organization of water in a hydrogel. In this study, the simplest model which could explain all of the results from the different thermal analysis techniques was one which consisted of three classes of water: (i) hydration water in close proximity to the polymer; (ii) interstitial water in regions or cavities surrounded by polymer chains; and (iii) bulk water.     

荧光导电聚合物聚N-[5-(8-羟基喹啉)甲基]苯胺的合成与表征

用化学氧化法合成了功能材料聚N-[5-(8-羟基喹啉)甲基]苯胺,并用X射线衍射、红外光谱、紫外-可见光谱和荧光分光光度计等对其及掺杂态结构和性质进行了表征和分析,研究结果表明该导电化合物无论掺杂与否,都同时既具有较好的导电性,又具有较好的荧光特性。     

The release of 5-fluorouracil from microspheres of poly(epsilon-caprolactone-co-ethylene oxide)

The purpose of this study was to evaluate the in vitro release of 5-fluorouracil from microspheres prepared using a novel triblock copolymer of ε-caprolactone and ethylene oxide as the encapsulating material. Microspheres of poly(ε-caprolactone-co-ethylene oxide) were prepared by employing the “hot-melt” method of microencapsulation. Microspheres were sized using sieve analysis and scanning electron microscopy (SEM). Release studies were performed using a custom-made rotating paddle dissolution apparatus. Copolymer microspheres, fabricated by the hot melt method were shown by electron microscopy to have smooth, nonporous surfaces. Drug-loaded microspheres were found to have a broad distribution of sizes, which was thought to be a consequence of the wide range of crystal sizes of the encapsulated unmilled drug. Nonlinear release kinetics were observed from microspheres in the size fraction 75-250 μm, with a pronounced “burst release” associated with the presence of drug at the surface of the microspheres. A specific delineation of the drug release mechanism was not possible due to rapid gelation, swelling, and subsequent dissolution of the microspheres that occurred on hydration. This work describes the preparation of microspheres that swell rapidly and coalesce together on hydration, accompanied by rapid drug release and copolymer dissolution over a 2-hr period.