pH-sensitive Poly Research Articles

Easy reversible clustering of gold nanoparticles via pH-Induced assembly of PVP-b-PAA copolymer

The growing demand of novel hybrid organic/inorganic systems with exciting properties has contributed to an increasing need for simplifying production strategies. Here, we report a simple method to obtain controlled three-dimensional hybrid architectures, in particular hybrid supracolloids (hSC), formed by gold nanoparticles and a double hydrophilic block copolymer, specifically the poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP), directly in aqueous medium. The ubiquitous pH-sensitive poly(acrylic acid) (PAA) block initiates the assembly through pH changes, while the poly(N-vinyl-2-pyrrolidone) block assures the close affinity with the AuNPs. We demonstrate that the formation of hybrid supracolloids (hSC) is the result of the synergetic behavior of the two specific polymeric blocks. Additionally, the entire process shows spontaneous and fast switchability. The nanostructured copolymer behaves like a highly swollen hydrogel and displays a disordered internal structure. The driving force for the association of the copolymer chains is induced by the synergetic effects of the decrease in solubility of the poly(acrylic acid) block and the formation of inter and intra chains hydrogen bonds. These were demonstrated by using small angle X-ray scattering (SAXS), quartz crystal microbalance with dissipation monitoring (QCM-D) and scanning transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (STEM-EDX). In turn, the AuNPs are randomly spread all over the polymeric matrix, as demonstrated by field emission gun – scanning electron microscopy (FEG-SEM). A correlation analysis reveals the hSC density depends mostly on the initial concentration of AuNPs. These results can inspire the fabrication of more complex structures with multicomponent composition.

Improved camptothecin encapsulation and efficacy by environmentally sensitive block copolymer/chitosan/fucoidan nanoparticles for targeting lung cancer cells

In this study, thermo-sensitive poly(N-isopropyl acrylamide) (PNP) was polymerized with pH-sensitive poly(acrylic acid) (PAA) to prepare a PAA-b-PNP block copolymer. Above its cloud point, the block copolymer self-assembled into nanoparticles (NPs), encapsulating the anticancer drug camptothecin (CPT) in situ. Chitosan (CS) and fucoidan (Fu) further modified these NPs, forming Fu-CPT-NPs to enhance biocompatibility, drug encapsulation efficiency (EE), and loading content (LC), crucially facilitating P-selectin targeting of lung cancer cells through a drug delivery system. The EE and LC reached 82 % and 3.5 %, respectively. According to transmission electron microscope observation, these Fu-CPT-NPs had uniform spherical shapes with an average diameter of ca. 250 nm. They could maintain their stability in a pH range of 5.0–6.8. In vitro experimental results revealed that the Fu-CPT-NPs exhibited good biocompatibility and had anticancer activity after encapsulating CPT. It could deliver CPT to cancer cells by targeting P-selectin, effectively increasing cell uptake and inducing cell apoptosis. Animal study results showed that the Fu-CPT-NPs inhibited lung tumor growth by increasing tumor cell apoptosis without causing significant tissue damage related to generating reactive oxygen species in lung cancer cells. This system can effectively improve drug-delivery efficiency and treatment effects and has great potential for treating lung cancer.

Colloidal and Biological Characterization of Dual Drug-Loaded Smart Micellar Systems.

Smart polymeric micelles (PMs) are of great interest in drug delivery owing to their low critical micellar concentration and sizes. In the present study, two different pH-sensitive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) copolymer samples were used for the encapsulation of paclitaxel (PTX), ursolic acid (UA), and dual loading of PTX and UA. Based on the molecular features of copolymers, spherical PMs with sizes of around 35 nm and 140 nm were obtained by dialysis for P2VP55-b-PEO284 and P2VP274-b-PEO1406 samples, respectively. The micellar sizes increased after loading of both drugs. Moreover, drug encapsulation and loading efficiencies varied from 53 to 94% and from 3.2 to 18.7% as a function of the copolymer/drug ratio, molar mass of copolymer sample, and drug type. By FT-IR spectroscopy, it was possible to demonstrate the drug loading and the presence of some interactions between the polymer matrix and loaded drugs. In vitro viability was studied on 4T1 mammary carcinoma mouse cells as a function of time and concentration of drug-loaded PMs. UA-PMs and free PMs alone were not effective in inhibiting the tumor cell growth whereas a viability of 40% was determined for cells treated with both PTX- and PTX/UA-loaded PMs. A synergic effect was noticed for PTX/UA-loaded PMs.

Block sequence dependent self-assembly and optoelectronic behavior of thermo- and pH-sensitive Polythiophene-graft-[Poly(diethylene glycol methyl ether methacrylate)-block-Poly(dimethyl amino ethyl methacrylate)] copolymers

To overcome the difficulty of using multistep process we report an one pot synthesis of polythiophene (PT)-graft block copolymers with thermo-sensitive poly(diethyleneglycol methyl ether methacrylate)(PDEGMEM) and pH-sensitive poly(dimethyl amino ethyl methacrylate)(PDMAEMA) using ATRP technique. The polymers PT-g-(PDEGMEM10-b-PDMAEMA3) (P1), PT-g-(PDMAEMA10-b-PDEGMEM3) (P2) and PT-g-(PDMAEMA6-ran-PDEGMEM8) (P3) are characterized by 1H NMR and SEC techniques. HRTEM study shows that P1 and P3 exhibit micellar morphology but P2 shows vesicular morphology, all sizes increase with increasing pH and temperature. UV–vis absorption spectra show pH, temperature and sequence dependent absorbance peak, and dc-conductivity (P2 > P3 > P1) indicates semi-conducting nature. Current-Voltage (I-V) property shows pH dependent memory and OMEIC property following above order. At pH3, on irradiation with white light the photocurrent gains of P2, P3 and P1 are 7.9, 6.6 and 3.5, respectively. Thus PT-graft block copolymers exhibit tunable self-assembly, optoelectronic, transport and photocurrent properties depending on proximity and preponderance of block sequence from PT backbone and also for their pH and thermo-responsivity.

Preparation of pH-sensitive nanogels bioconjugated with shark antibodies (VNAR) for targeted drug delivery with potential applications in colon cancer therapies.

Cancer is the second leading cause of death worldwide. To combat this disease, novel and specialized therapeutic systems are urgently needed. This is the first study to explore a system that combines shark variable domain (Fv) of new antigen receptor (VNAR) antibodies (hereinafter VNARs), PEGylated nanogels (pH-sensitive poly(N,N-diethylaminoethyl methacrylate, PDEAEM), and the anticancer drug 5-fluorouracil (5-FU) to explore its potential applications in colon cancer therapies. Nanogels were functionalized in a scalable reaction with an N-hydroxysuccinimide (NHS)-terminated polyethylene glycol derivative and bioconjugated with shark antibodies. Dynamic light scattering measurements indicated the presence of monodispersed nanogels (74 to 236 nm). All systems maintained the pH-sensitive capacity to increase in size as pH decreased. This has direct implications for the release kinetics of 5-FU, which was released faster at pH 5 than at pH 7.4. After bioconjugation, the ELISA results indicated VNAR presence and carcinoembryonic antigen (CEA) recognition. In vitro evaluations of HCT-116 colon cancer cells indicated that functionalized empty nanogels are not cytotoxic and when loaded with 5-FU, the cytotoxic effect of the drug is preserved. A 15% reduction in cell viability was observed after two hours of contact with bioconjugated nanogels when compared to what was observed with non-bioconjugated nanogels. The prepared nanogel system shows potential as an effective and site-specific nanocarrier with promising applications in in vivo studies of colon cancer therapies.

PEGylated insulin loaded complexation hydrogels for protected oral delivery

While a number of enteric coatings and pH-sensitive oral delivery vehicles have been developed, they lack the ability to sufficiently protect proteins from proteolytic degradation once released from the carrier. In this work, we show that H-bonded, pH-sensitive poly(methacrylic acid-grafted ethylene glycol) glycol (henceforth designated as P(MAA-g-EG) gels) exhibit great promise as protein carriers, as they utilize poly(ethylene glycol) (PEG) chains to promote mucoadhesion in the small intestine, increasing the chances that the drug is released within the villus of the absorptive intestinal wall. Importantly, PEG was also conjugated to the B29-lysine (LysB29) position of insulin in order to protect the drug from proteolytic degradation once released in the small intestine and adhere the drug to the intestinal epithelium through improved mucoadhesion. PEG-conjugated (PEGylated) molecules were found to actively participate in the carrier loading and release mechanism, with the drug conjugate hydrogen bonding to the MAA while in the collapsed state and subsequently repulse the drug above the polymer's isoelectric point. This effect was enhanced through the evaluation of PEG graft density within the carrier. Cellular transport and changes in transepithelial resistance caused by the PEGylated insulin (PI) in the presence of P(MAA-g-EG) microparticles were analyzed using a 1:1 co-culture of human colon adenocarcinoma (Caco-2) and: the mucus-secreting human colon carcinoma cell(HT-29-MTX). Finally, the in vivo absorption of insulin was measured in Sprague-Dawley rats to ensure that the PEGylated insulin conjugates are biologically active, as well as to compare the bioavailability to control insulin. Collectively, these results lead toward the development of a novel system for improved insulin delivery, with improved stability of insulin through PEGylation.

Formulation of double nanoemulsions based on pH-sensitive poly acrylic acid/agarose/ZnO for quercetin controlled release

Quercetin (QC) is a promising cancer drug, though its poor solubility and quick release reduce its bioavailability, thus limiting its current applications. In this research, a new hydrogel nanocomposite comprising zinc oxide nanoparticles (ZnONPs), agarose, and polyacrylic acid (PAA), was designed to load QC. Spherical nanocarriers were prepared via environmentally friendly and simple double emulsion approach by injecting PAA/Aga/ZnONPs coated by SPAN 80 surfactant to a hydrophobic olive oil phase. The nanoemulsions were characterized by different techniques to assess the impact of ZnONPs on PAA/Aga pH-sensitive hydrogel as a novel platform for direct administration of QC. FTIR and XRD analysis confirmed the presence of all the nanocomposite components in the final formulation. FE-SEM images revealed the spherical shape and surface homogeneity of the nanocarriers, and zeta potential measurements corroborated their colloidal stability. The addition of ZnONPS increased the drug loading from 41.25% to 47.50% and the encapsulation efficiency from 83.0% to 87.25%. A slower drug release was observed at pH 7.4 for periods of time shorter than 96 h, corroborating the pH-sensitivity of the nanoemulsions. Drug release data at pH 5.4 fitted well to the First-order equation, while at pH 7.4 were better described by the Korsmeyer Peppas model. The reduction in MCF7 living cells in the presence of PAA/Aga/ZnONPs compared to PAA/Aga and the control sample indicates the in vitro cytotoxicity of ZnONPs. The number of late apoptotic cells in PAA/Aga/ZnONPs/QC (37.55%) was higher than that of the other formulations (ZnONPs, PAA/Aga and PAA/Aga/ZnONPs), which may be due to the controlled and slow release of QC from PAA/Aga/ZnONPs/QC. Therefore, these green, biocompatible and biodegradable nanoemulsions show great potential as nanocarriers for QC loading and sustained release against breast cancer.

PH-Sensitive Poly(acrylic acid)-g-poly(L-lysine) Charge-Driven Self-Assembling Hydrogels with 3D-Printability and Self-Healing Properties.

We report the rheological behavior of aqueous solutions of a graft copolymer polyampholyte, constituted of polyacrylic acid (PAA) backbone grafted by Poly(L-lysine) (PAA-b-PLL). The graft copolymer self-assembles in aqueous media, forming a three-dimensional (3D) network through polyelectrolyte complexation of the oppositely charged PAA and PLL segments. Rheological investigations showed that the hydrogel exhibits interesting properties, namely, relatively low critical gel concentration, elastic response with slow dynamics, remarkable extended critical strain to flow, shear responsiveness, injectability, 3D printability and self-healing. Due to the weak nature of the involved polyelectrolyte segments, the hydrogel properties display pH-dependency, and they are affected by the presence of salt. Especially upon varying pH, the PLL secondary structure changes from random coil to α-helix, affecting the crosslinking structural mode and, in turn, the overall network structure as reflected in the rheological properties. Thanks to the biocompatibility of the copolymer constituents and the biodegradability of PLL, the designed gelator seems to exhibit potential for bioapplications.

Dispersion Performances of Naphthalimides Doped in Dual Temperature- and pH-Sensitive Poly (N-Isopropylacrylamide-co-acrylic Acid) Shell Assembled with Vinyl-Modified Mesoporous SiO2 Core for Fluorescence Cell Imaging.

Developing effective intelligent nanocarriers is highly desirable for fluorescence imaging and therapeutic applications but remains challenging. Using a vinyl-grafted BMMs (bimodal mesoporous SiO2 materials) as a core and PAN ((2-aminoethyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione))-dispersed dual pH/thermal-sensitive poly(N-isopropylacrylamide-co-acrylic acid) as a shell, PAN@BMMs with strong fluorescence and good dispersibility were prepared. Their mesoporous features and physicochemical properties were extensively characterized via XRD patterns, N2 adsorption-desorption analysis, SEM/TEM images, TGA profiles, and FT-IR spectra. In particular, their mass fractal dimension (dm) features based on SAXS patterns combined with fluorescence spectra were successfully obtained to evaluate the uniformity of the fluorescence dispersions, showing that the dm values increased from 2.49 to 2.70 with an increase of the AN-additive amount from 0.05 to 1%, along with the red shifting of their fluorescent emission wavelength from 471 to 488 nm. The composite (PAN@BMMs-I-0.1) presented a densification trend and a slight decrease in peak (490 nm) intensity during the shrinking process. Its fluorescent decay profiles confirmed two fluorescence lifetimes of 3.59 and 10.62 ns. The low cytotoxicity obtained via in vitro cell survival assay and the efficient green imaging performed via HeLa cell internalization suggested that the smart PAN@BMM composites are potential carriers for in vivo imaging and therapy.

Delivery of nitric oxide with a pH-responsive nanocarrier for the treatment of renal fibrosis

Fibrosis is an excessive accumulation of extracellular matrix (ECM) that may cause severe organ dysfunction. Nitric oxide (NO), a multifunctional gaseous signaling molecule, may inhibit fibrosis, and delivery of NO may serve as a potential antifibrotic strategy. However, major limitations in the application of NO to treat fibrotic diseases include its nonspecificity, short half-life and low availability in fibrotic tissue. Herein, we aimed to develop a stimuli-responsive drug carrier to deliver NO to halt kidney fibrosis. We manufactured a nanoparticle (NP) composed of pH-sensitive poly[2-(diisopropylamino)ethyl methacrylate (PDPA) polymers to encapsulate a NO donor, a dinitrosyl iron complex (DNIC; [Fe2(μ-SEt)2(NO)4]). The NPs were stable at physiological pH7.4 but disintegrated at pH4.0-6.0. The NPs showed significant cytotoxicity to cultured human myofibroblasts and were able to inhibit the activation of myofibroblasts, as indicated by a lower expression level of α-smooth muscle actin and the synthesis of a major ECM component, collagen I, in cultured human myofibroblasts. When given to mice treated with unilateral ureteral ligation/obstruction (UUO) to induce kidney fibrosis, these NPs remained in blood at a stable concentration for as long as 24h and might enter the fibrotic kidneys to suppress myofibroblast activation and collagen I production, leading to a 70% reduction in the fibrotic area. In summary, our strategy to assemble a NO donor, the iron nitrosyl complex DNIC, into pH-responsive NPs proves effective in treating renal fibrosis and warrants further investigation for its therapeutic potential.

Multi-fractal modeling of curcumin release mechanism from polymeric nanomicelles

The physicochemical properties of “smart” or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system’s nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process.

Temperature/pH-Sensitive Double Cross-Linked Hydrogels as Platform for Controlled Delivery of Metoclopramide.

Novel double cross-linked (DC) hydrogels with pH-/temperature-sensitive properties were designed and developed. Therefore, linear pH-sensitive poly(methyl vinyl ether-alt-maleic acid) (P(VME/MA)) macromolecules were absorbed within a thermosensitive poly(N-isopropylacrylamide-co-hydroxyethylacrylamide)-hydrogel (PNH) and, subsequently, cross-linked together through a solvent-free thermal method. As a novelty, double cross-linked hydrogels were obtained from previously purified polymers in the absence of any solvent or cross-linking agent, which are generally harmful for the body. The new DC structures were characterized by FT-IR spectroscopy, SEM, swelling kinetic measurements, and mechanical tests. The resulting scaffolds exhibited interconnected pores and a flexible pattern, compared to the brittle structure of conventional PNH. The swelling kinetics of DC hydrogels were deeply affected by temperature (25 and 37 °C) and pH (7.4 and 1.2). Furthermore, the hydrogels absorbed a great amount of water in a basic environment and displayed improved mechanical properties. Metoclopramide (Met) was loaded within DC hydrogels as a model drug to investigate the ability of the support to control the drug release rate. The results obtained recommended them as convenient platforms for the oral administration of drugs, with the release of the largest part of the active principle occurring in the colon.

Synthesis of pH sensitive microcapsules containing ZAPP, SAPP, and 8-HQ, and evaluation of their anti-corrosion performance, and mechanical enhancement of epoxy coating

Self-healing coatings containing microcapsules have a remarkable ability to preserve metal surfaces for a long time, which is why these smart coatings have received a lot of attention. In this study, pH-sensitive poly melamine-formaldehyde microcapsules were synthesized by in-situ polymerization and loaded into the epoxy coating. 8-HQ, ZAPP, and SAPP were used as inhibitors in the core of microcapsules (named MF8HQ, MFZAPP, and MFSAPP, respectively). The microcapsules were synthesized at different stirring times and rates to obtain the optimum state (800 rpm and 2.5 h), then characterized by SEM, TEM, and FT-IR tests. Also, the mechanical properties of coatings with different weight percentages of loaded microcapsules were investigated using tensile measurement, DMTA, and Pull-off tests. The results revealed that the presence of 5 wt% of microcapsules in coatings is along with more appropriate Tg, modulus, and adhesion strength compared to more or fewer amounts. Also, EIS and salt spray tests were used to evaluate the anti-corrosion properties of the coating. The results suggested that epoxy coating containing MF8HQ showed the best anti-corrosion performance after 35 days of immersion in 3.5 wt% of NaCl solution (delamination index = 45.7 %), followed by MFZAPP (delamination index = 69.5 %) and MFSAPP performance (delamination index = 84.2 %) which were better than neat epoxy, respectively. Finally, the Quantum analysis was used to ensure the 8-HQ inhibitory performance and analyze the mechanism of inhibiting action at the interface.

Dynamic crosslinked polymeric nano-prodrugs for highly selective synergistic chemotherapy

To achieve highly selective synergistic chemotherapy attractive for clinical translation, the precise polymeric nano-prodrugs (PPD-NPs) were successfully constructed via the facile crosslinking reaction between pH-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug (Pt(IV)-1). PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin (DMC). Moreover, PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure, suitable negative potentials and low critical micelle concentration (CMC), improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular pH, promoted efficient disintegration and drug release at tumoural intracellular pH/glutathione, and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2, achieving significant tumour suppression while decreasing the side effects. Thus, the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.

Intracellular transport of biomacromolecular drugs by a designed microgel capsule with pH/redox stimulus-responsiveness

Biological macromolecular drugs usually have good efficacy and recognition performance. However, due to their large molecular weight and easy degradation/inactivation, general carriers are difficult to transport them into cell stably and safely. Here, a pH/redox dual-responsive microgel capsule was prepared for constructing a double-locked drug delivery system. Firstly, the pH-sensitive poly(ethyleneimine)-block-poly(2-(diisopropylamino ethylmethacry-late)-block-poly(ethyleneimine) triblock copolymers (PEI-PDPA-PEI) were synthesized for preparing polymer vesicles. The PEI layer was crosslinked by disulfide groups to finally obtain pH/redox dual-responsive microgel capsule, marked as P-VesicleGEL. Then, the P-VesicleGEL was used to encapsulate different types of drugs (doxorubicin hydrochloride, rhodamine, proteins, aptamer), and had a higher loading capacity than the corresponding polymer micelles for macromolecules. Compared with small molecules, P-VesicleGEL had much better "double-locked" function for macromolecules. I.e., only when the two “locks” were opened simultaneously the release could be triggered. Furtherly, cell experiments had proved that the P-VesicleGEL had excellent biocompatibility and cell transfection ability. It could not only effectively identify normal and cancer cells, but also transport biological drugs that were difficult to enter into cells by themselves. The microgel capsule designed here is expected to be applied for the intracellular delivery/release of biological macromolecular drugs.

Characterization of active and pH-sensitive poly(lactic acid) (PLA)/nanofibrillated cellulose (NFC) films containing essential oils and anthocyanin for food packaging application

Active and pH-sensitive films of poly(lactic acid) (PLA)/nanofibrillated cellulose (NFC) have been fabricated and tested. The PLA and PLA/NFC films with 1.5% NFC were prepared via solvent casting method, with different loadings of essential oil (EO), including thymol and curry, being added at 5, 10, and 15%. The fixed content of anthocyanin powder (1%) was incorporated into the films as a pH indicator. The active PLA and PLA/NFC films were characterised on their physical, mechanical, thermal, and biodegradation properties. The addition of NFC reduced the tensile strength but increased the flexibility of films due to the plasticizing effect of EOs. The PLA/EO and PLA/NFC/EO films containing curry demonstrated a slightly higher strength than the films with thymol. The flexibility of films was increased at higher loading of EO regardless of the types of EO. The thermal profile demonstrated that the neat PLA film had a higher maximum degradation temperature than the active PLA/EO and PLA/NFC/EO films. The active PLA/EO and PLA/NFC/EO films containing anthocyanin successfully changed its colour in pH 2.0 and 14.0. The PLA/NFC films with thymol and anthocyanin formulation could inhibit fungus growth better in the cherry tomato sample than the PLA/NFC films with curry and anthocyanin.

Study on release and inhibition action of mixed ZAPP and 8-HQ corrosion inhibitors loaded in pH-sensitive microcapsules for Mg AZ31

In-situ polymerization was used to synthesize pH-sensitive poly melamine-formaldehyde (PPMF)11pH-sensitive poly melamine-formaldehyde microcapsules containing 8-HQ228-Hydroxyquinoline and ZAPP33Zinc aluminum polyphosphate inhibitors. The chemical structure of PPMF microcapsules was confirmed using FTIR44Fourier transform infra-red spectroscopy, the mean particle size (2 µm) was determined using DLS55Diffraction light scattering, and the rough shape of the microcapsules was investigated using FESEM66Field-emission scanning electron microscopy. UV–visible spectroscopy77Ultraviolet-visible, EDX88Energy-dispersive x-ray spectroscopy, and ICP99Inductively coupled plasma were used to investigate inhibitors' release. The corrosion inhibition in coatings containing mixed encapsulated 8-HQ and ZAPP was suggested by the EIS1010Electrochemical impedance spectroscopy in 3.5 wt% NaCl solution by forming a protective layer, resulting in a significant increase in charge transfer and diffusion resistance, confirming the synergistic effect of mixed inhibitors. According to EIS measurements, long-lasting coatings (RCT= 16.8 MOhm.cm2 after 10 weeks) were produced by adding PPMF microcapsules containing mixed corrosion inhibitors due mainly to smart inhibitor release.

PH-Sensitive poly (acrylic acid-co-acrylamide) anionic hydrogels for jejunum targeted drug delivery systems

pH-Sensitive poly (acrylic acid-co-acrylamide) anionic hydrogels for jejunum targeted drug delivery systems

Hydrophilic drug release from electrospun membranes made out of thermo and pH-sensitive polymers

Electrospun fibers of the thermo-and pH sensitive poly(N-vinylcaprolactam-co-acrylic acid) (Poly(NVCL-co-AA) loaded with 10% and 30 wt% caffeine (Caf) were obtained by electrospinning and evaluated as potential drug delivery systems. Caffeine was used as a hydrophilic drug model, and poly(NVCL-co-AA) containing either 20 or 30 mol% AA was used as a carrier. The fibers morphology, as well as, their interaction with caffeine, were studied using different analytical techniques. The cytotoxicity of the different obtained fibers was evaluated by cell viability assays using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and mouse embryonic fibroblasts cell line (MEF cells). Caffeine release was studied at temperatures of 25 °C and 42 °C and pH of 1.2 and 7.4. Beadless copolymer fibers with diameters ranging from 1 μm to 2 μm were obtained. The addition of caffeine, which was in crystalline form after being encapsulated in the fibers, resulted in an increase of fiber diameter. The obtained membranes were found to be not cytotoxic. The entrapment of caffeine was greater for the copolymer containing 30 mol% AA due to a greater affinity of AA to caffeine. At a pH of 1.2 and at both temperatures of 25 °C and 42 °C, as well as, at a pH of 7.4 and a temperature of 42 °C, a Fickian diffusion mechanism for all copolymer fiber mats was observed. At a pH of 7.4 and 25 °C the release profile showed a high rate and followed a zero-order model, due to the fast dissolution of caffeine in water. These results indicated that thermo-and pH-sensitive poly(NVCL-co-AA) are promising candidates for controlled release of hydrophilic drugs.

PH and Temperature Double-Switch Hybrid Micelles for Controllable Drug Release.

pH/temperature dual-responsive hybrid micelles were prepared for constructing a double-locked drug delivery system. The temperature-sensitive polyethylene glycol-poly(tetrahydropyranylmethacrylate)-polyethylene glycol (PEG-PTHPMA-PEG) triblock copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization and amide coupling reaction. pH-sensitive poly(2-(diisopropylamino ethylmethacrylate)-polyethylene glycol (PDPA-PEG) diblock polymers were introduced, which could self-assemble with PEG-PTHPMA-PEG in aqueous solutions to form hybrid micelles. The anticancer drug doxorubicin, which was encapsulated in the core of the hybrid micelles, could be released only under simultaneous stimulations of pH and temperature. It was proved that the micelles could maintain their structural stability under a unilateral stimulus, while the structure collapsed and recombined under a double stimulus, which triggered a large amount of drug release. Furthermore, the excellent biocompatibility and dual sensitivity of the vector were also proved by cytotoxicity experiments. The dual-responsive hybrid micelles designed here showed the advantages of a double insurance lock of drug leakage and precise controllability of drug release, which could act as accurate drug delivery systems.