Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH- and H₂O₂-responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch, has been developed to achieve self-regulated administration. The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] (PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H₂O₂ and pH stimuli due to the chemical change of H₂O₂ sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase (GOx, which can oxidize glucose to gluconic acid and in-situ produce H₂O₂) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Synthesis of hollow mesoporous silica (HMS) nanoparticles as a candidate for sulfasalazine drug loading

Hollow mesoporous silica nanoparticles have emerged as attractive drug delivery carriers. In this work, we report successful synthesis of hollow mesoporous silica nanoparticles (HMSNs) using poly tert-butyl acrylate (PtBA) nanospheres as hard templates and CTAB as structure directing agent for loading sulfasalazine into its porous structure. The samples were synthesized using PtBA; sodium dodecyl sulfate (SDS) - in an aqueous solution of CTAB and tetraethylorthosilicate (TEOS) as the inorganic precursor. Two different methods were utilized to remove organic phases including calcination, and acidic/basic ethanolic solvent extraction approach. For the latter, microstructural studies using SEM and N₂ porosimetery revealed the formation of highly uniform mono-dispersed particles of sphere morphology (~ 130 nm) with the high specific surface area (1501 m²/g) and mean pore size of ~ 2.6 nm. However, rather deformed and aggregated sphere-like particles were obtained for the calcined samples. TEM examinations also confirmed the formation of 20–30 nm thick walls for the prepared HMSNs particles. Further, HMSN samples treated by solvent extraction method were functionalized by 3-aminopropyl triethoxysilane (APTS) compound for drug delivery. DTA/TG analysis showed that the total amount of loaded sulfasalazine drug was 5.1 wt%.     

Indomethacin release behaviors from pH and thermoresponsive poly(vinyl alcohol) and poly(acrylic acid) IPN hydrogels for site-specific drug delivery

A temperature- and pH-responsive drug delivery system was studied by using interpenetrating polymer network (IPN) hydrogels constructed with poly(acrylic acid) (PAAc) and poly(vinyl alcohol) (PVA). The release of indomethacin incorporated into these hydrogels showed pulsatile patterns in response to both pH and temperature. Indomethacin diffused from the polymer matrices through the swelling and deswelling mechanism. The release amount increased at higher temperature because of the swelling caused by the dissociation of hydrogen bonding. The drastic change of drug release was achieved by alternating pH of the buffer solution and was attributed to the change of states of ionic groups within IPN hydrogels. The free water contents were calculated by using differential scanning calorimetry (DSC), and were proved to be the main factor in the swelling. These results demonstrated that the drug release could be controlled by the swelling/deswelling degree of IPN hydrogels as functions of pH and/or temperature. © 1997 John Wiley & Sons, Inc. J Appl Polm Sci 65: 685–693     

氧化石墨烯纳米粒子提高乳化酸性能实验研究

为了提高乳化酸在中高温油藏的深部酸化效果,将酸性条件下能够稳定存在的氧化石墨烯纳米粒子与表面活性剂复配使用。通过二者的协同效应提高界面膜的稳定性,从而提高乳化酸的稳定性和酸化选择能力。所开发的纳米乳化酸的配比为:0.8%氧化石墨烯纳米粒子+24%HCl+29%0#柴油+0.4%Span80+0.1%烷基胺+0.3%缓蚀剂+0.2%铁离子稳定剂+水。对比不含纳米粒子的乳化酸,该纳米乳化酸在地层中的酸岩反应要滞后120 min左右、对酸岩反应的缓速能力更强、酸化选择性能强,经含氧化石墨烯纳米粒子乳化酸冲刷后的岩石表面已成油湿。实验表明氧化石墨烯纳米材料可较好地用于乳化酸体系,为乳化酸产品的开发提供重要支撑。     

Fe3O4/poly(acrylic acid) hybrid nanoparticles for water‐based drilling fluids

Because of the sizes of the pore throat are on the nanometer scale, nanoparticles with sizes on the nanoscale have been developed as candidates for plugging materials during drilling in shale formation. In this study, Fe₃O₄ nanoparticles were prepared by a coprecipitation method, and then, Fe₃O₄/poly(acrylic acid) (PAA) hybrid nanoparticles were obtained through the modification of the Fe₃O₄ nanoparticles with PAA. The hybrid nanoparticles were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, and thermogravimetric analysis. The magnetic properties, salt tolerance, and compatibility with sulfomethylated phenolic resin of the nanoparticles were studied. The plugging properties of the Fe₃O₄/PAA hybrid nanoparticles were evaluated by filtration testing of the filter cakes at ambient temperature and 80 °C. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43967.     

Delivery of PEGylated drugs from mucoadhesive formulations by pH-induced disruption of H-bonded complexes of PEG-drug with poly(acrylic acid)

We formed viscous, mucoadhesive gels by complexing PEGylated proteins with poly(acrylic acid) (PAA) at pH 3. These complexes dissociate at pH 7.4, and under this condition the PEGylated protein is released from the gel. We propose this system as a means for prolonged mucosal delivery of a PEGylated protein to nasal, ophthalmic or vaginal sites. In this paper we have studied the effect of the molecular weight of the PEG used in the PEGylated protein (5 kD, 20 kD and 40 kD PEG) and the effect of added free PEG (18.5 kD) on the in vitro release rate of the PEGylated protein from complexes with PAA. The PEGylated proteins we studied included papain, MW = 23.7 kD and pI 8.75, and soybean trypsin inhibitor (STI), MW = 20.1 kD and pI 4.6.     

A mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poly(vinyl alcohol) for mucosal drug delivery

The interpolymer complexes composed of PVA and PAA were prepared by template polymerization of acrylic acid in the presence of PVA with different molecular weights and degrees of saponification. The carbonyl absorption band of the PAA in the PAA/PVA interpolymer complexes was shifted to a lower wavenumber due to H‐bonding between the carboxyl group of PAA and the hydroxyl group of PVA. The swelling ratio and the degree of dissolution of the PVA/PAA interpolymer complexes were dependent on the pH of the medium, the molecular weight, and the degree of saponification of the PVA. The release rate of a model drug, lidocaine, from the complexes decreased with increasing degree of saponification of the PVA due to the lower swelling degree of the complex. The adhesive force of the PVA/PAA interpolymer complexes with a plastic plate (poly propylene) was stronger than that of the commercial Carbopol 971P. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 327–331, 2004     

Tuned interactions of silver nanoparticles with ZSM-5 zeolite by adhesion-promoting poly(acrylic acid) deposited by electrospray ionization (ESI)

The electrospray ionization (ESI) method was used for deposition of thin films of poly(acrylic acid) (PAA) on Cu/ZSM-5 (5 wt.% Cu) and Ag–Cu/ZSM-5 (1 wt.% Ag and 4 wt.% Cu) composites. For comparative purposes, the ZSM-5 zeolite was synthesized under hydrothermal conditions and loaded with PAA under the same treating conditions as the composites. This method allowed the formation of uniform polymer films of controlled thickness on conductive substrates. The structural characteristics were characterized by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, atomic force microscopy and X-ray diffraction (XRD). The deposited PAA layer over ZSM-5 acts as a common dispersing and stabilizing agent through coordination-driven guest-templated polymer via interaction of Ag⁺ and Cu²⁺ with carboxylic acid groups, thus increasing and controlling the adhesion and the release of metallic species. A short exposure to light and temperature has reduced the metal ions to Cu⁰ and Ag⁰ metallic nanoparticles. The results of XRD analysis let suggest that the interaction of Cu and Ag with carboxylic groups of PAA inhibits the formation of large metallic silver particles. These samples were being studied for their potential as antibacterial agents toward the bacterial strains such as Staphylococcus pneumonia, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa as Gram positive and Gram negative bacteria, respectively. Aspergillus fumigatus and Candida albicans as Fungi were also evaluated. The Cu/ZSM-5 and Ag–Cu/ZSM-5 nanocomposites coated with a 10 nm thick PAA layer exhibit significant antibacterial activity.     

Study of thermomechanical,structural and antibacterial properties of poly(lactic acid) reinforced with graphene oxide nanoparticles via melt mixing

Addition of graphene oxide (GO) to poly(l ‐lactic acid) (PLLA) offers an alternative approach for tuning its crystallinity, improving its mechanical properties and transfusing an antibacterial behavior. GO/PLLA nanocomposites were prepared by melt extrusion, thus avoiding the potentially toxic, for biomedical applications, residue of organic solvents. Fourier transform infrared spectroscopy verified the formation of intermolecular hydrogen bonds. Using differential scanning calorimetry experiments concerning the isothermal crystallization of PLLA and PLLA containing 0.4 wt% GO, a two‐dimensional disc‐like geometry of crystal growth was determined, whereas at 125 and 130 °C the nanocomposite developed three‐dimensional spherulitic growth. Higher crystallization rate constant values suggest that the incorporation of 0.4 wt% GO accelerated the crystallization of PLLA. The lowest crystallization half‐time for PLLA was observed at 115 °C, while at 110 °C GO caused its highest decrease, accompanied by the highest increase in melting enthalpy (ΔH_m), as compared to that of PLLA, after completion of isothermal crystallization. Their ΔH_m values increased with T_ic, whereas multiple melting peaks transited to a single one with increasing T_ic. GO improved the PLLA thermal stability, tensile strength and Young's modulus. Incorporation of 0.8 wt% GO endowed PLLA with another potential application as a biomaterial since the derived composite presented good thermomechanical properties and effective prohibition of Escherichia coli bacteria attachment and proliferation. This effect was more prominent under simulated sunlight exposure than in the dark. The preparation method did not compromise the intrinsic properties of GO. © 2020 Society of Chemical Industry     

Drug delivery system based on poly(ether‐block‐amide) and acrylic acid for controlled release of vancomycin

Poly(ether‐block‐amide) (PEBA) films were grafted with acrylic acid (AAc) by gamma radiation, using the oxidative pre‐irradiation technique. The effect of dose, monomer concentration, temperature, and reaction time on the graft percentage of AAc onto PEBA was studied. The modified material PEBA‐g‐AAc was characterized by Fourier infrared spectroscopy (FTIR), scanning electron microscopy, and water contact angle. It was found that PEBA films did not suffer degradation at low doses (<30 kGy) during the grafting process. Additionally, PEBA‐g‐AAc was proved as drug delivery system using vancomycin as drug model. The PEBA‐g‐AAc with 39 and 98% of AAc loaded 63 and 98 mg g^?1, respectively. The release profiles showed a sustained delivery by 48 h with a partial retention of drug, which depends of grafting percentage. The microbiological tests showed that PEBA‐g‐AAc was able to inhibit the growing of Staphylococcus aureus in three consecutive challenges. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45745.     

Change in the molecular weight distribution of poly(ethylene oxide) caused by the complexation with poly(acrylic acid)

The complexation between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) was made by using double the molar quantity of either polymer component at pH 2 where the resulting complex completely precipitates. After the removal of the precipitate, PEO or PAA remaining in the supernatant was subjected to gel permeation chromatography to investigate the change in the molecular weight distribution (MWD) caused by the complexation. No remarkable difference is observed in the MWD curves for PEO[1] (M_w=1.37 × 10⁴) before and after the complexation with PAA[1] (M_w=1.10 × 10³) and PAA[2] (M_w=4.16 × 10⁵). However, the MWD curves of PEO[2] (M_w=1.26 × 10⁵) and PAA[2] become shortened and shift to the low molecular weight side after the complexation with PAA[1] or [2] and PEO[2], respectively. This tendency is enhanced by increasing the complexation temperature. From these results, it is indicated that the complexation between PEO and PAA deals with an equilibrium reaction, and the equilibrium constant is dependent on the chain length of both polymer components and also on the complexation temperature.     

Production of new hybrid systems for drug delivery by PGSS (Particles from Gas Saturated Solutions) process

The formulation of S-(+)-ibuprofen as a model water-insoluble drug in different carrier materials (poloxamers, gelucire and glyceryl monostearate, GMS) by Particles from Gas Saturated Solutions (PGSS) technique has been studied. Porous, spherical particles of 50⿿200 μm have been obtained with encapsulation efficiencies up to 90%. Differential scanning calorimetry assays reveal modifications on the structure of the material, with formation of a solid solution in experiments with poloxamer carriers, and formation of solid dispersions with a possible reduction of the crystallinity of the carrier in experiments with GMS. Drug release tests in simulated gastric and intestinal fluids have been performed. Formulations with poloxamer carrier materials provided an increased solubility of ibuprofen in the gastrointestinal fluids, with a very fast release and dissolution of this compound, while gelucire and GMS carriers did not improve the solubility of ibuprofen, but provided a slower, controlled release of the drug. PGSS-processed samples presented a superior performance over physical mixtures in terms of the solubility increase and the control of the release rate. These results show the wide possibilities and flexibility of the PGSS technique for the development of hybrid formulations of water-insoluble active compounds with hydrophilic or hydrophobic carrier materials, achieving either an increased, accelerated dissolution, or a slower, controlled delivery, depending on the choice of carrier materials.     

Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Surface decoration of magnetic nanoparticles with folate-conjugated poly(N-isopropylacrylamide-co-itaconic acid): A facial synthesis of dual-responsive nanocarrier for targeted delivery of doxorubicin

The aim of study was to develop a novel drug nanocarrier via facile coating of a folate-conjugated dual-responsive copolymer with carboxylic functional groups on the surface of magnetic nanoparticles for the efficient loading and cell-specific targeting of a positively charged anticancer agent. The nanocarrier exhibited many favorable capabilities such as narrow distributed nano-ranged size (～30 nm), high drug loading capacity (～65%), and stimuli-responsive drug release. The results of various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry concluded that the developed smart nanocarrier paves a way for efficient cancer therapy by the multiple targeting strategies.     

In vitro and in vivo evaluation of poly(2-methoxyethyl methacrylate-co-acrylic acid)-based microhydrogels for pH-responsive targeted delivery of model drug

ABSTRACT

The study aimed to develop chemically crosslinked poly(2-methoxyethyl methacrylate-co-acrylic acid) (p(MEMA-co-AA)) microhydrogels as carriers for pH-responsive oral targeted delivery of therapeutics. p(MEMA-co-AA) microgels were successfully synthesized by simple free radical suspension polymerization technique confirmed through Fourier transform infrared spectroscopy, thermogravimetic analysis, powdered x-ray diffractrometry, and scanning electron microscopy. Chemically crosslinked spherical microhydrogels with an average size in the range of 4.1 µm ± 2.21 to 9.7 µm ± 3.21 exhibited pH-dependent controlled release of the model drug. Maximum swelling, drug loading, and release were observed at pH 7.4. The optimal formulation achieved good delayed and sustained release features with decreased C_max, prolonged T_max, and mean residence time in comparison to oral drug solution.     

Poly(D,L‐lactide‐co‐glycolide)/poly(ethylenimine) blend matrix system for pH sensitive drug delivery

Poly(D ,L ‐lactide‐co‐glycolide) (PLGA) and poly(ethylenimine) (PEI) were blended and found to form a homogeneous pH sensitive matrix for drug release. Differential scanning calorimetry (DSC) studies of the PLGA/PEI blends showed a single glass transition temperature at all compositions. Fourier transform infrared spectroscopy (FTIR) demonstrated that the PLGA carbonyl peak at 1760 cm^?1 shifted to 1666 cm^?1 as a result of amide bond formation between the two polymers. This was confirmed by ¹³C nuclear magnetic resonance studies. A PLGA/PEI matrix of 90/10 weight ratio was chosen for evaluation for controlled drug release. Both hydrophobic β‐lapachone and hydrophilic rhodamine B showed pH dependent release profiles with faster release kinetics at lower pH values. The observed pH sensitive drug release was mainly attributed to two factors, pH dependent swelling and protonation of the PEI‐PLGA matrix. These results demonstrate utility of a PLGA/PEI matrix and its potential application in pH responsive drug delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 89–96, 2006     

Photo/pH dual‐responsive biocompatible poly(methacrylic acid)‐based particles for triggered drug delivery

A novel dual‐responsive (light and pH) particle based on poly(methacrylic acid), poly(methacrylic acid)–poly[1‐(2‐nitrophenyl)ethane‐1,2‐diyl bis(2‐methylacrylate)]was prepared with the facile method of two‐step homogeneous radical polymerization with methacrylic acid as the monomer and 1‐(2‐nitrophenyl)ethane‐1,2‐diyl bis(2‐methylacrylate) as a photodegradable crosslinker. Photolytic assessments were conducted upon irradiation with a UV lamp; this led to particle disintegration caused by cleavage of the photolabile crosslinking points. The light‐dependent degradation was investigated through particle size changes, absorption spectra variations, surface morphology changes, Fourier transform infrared spectroscopy, and the release of Nile red from the particles after irradiation. The pH dependence of the particle systems induced by the protonation and deprotonation of poly(methacrylic acid) was also confirmed by fluorescence spectroscopy. The triggered release of fluorescein diacetate was investigated to demonstrate that the release behavior in cells was light dependent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44003.     

Fabrication of tough,self-recoverable,and electrically conductive hydrogels by in situ reduction of poly(acrylic acid) grafted graphene oxide in polyacrylamide hydrogel matrix

Developing electrically conductive hydrogels with good electronic properties and excellent mechanical performance is significant to their potential applications. In this article, we present a strategy to fabricate tough, self-recoverable and electrically conductive hydrogels containing reduced graphene oxide (rGO). Poly(acrylic acid) grafted graphene oxide (GO-g-PAA) was synthesized and incorporated into chemically crosslinked polyacrylamide (PAM) networks to obtain GO-g-PAA/PAM hydrogels, which were further treated with ascorbic acid solution at ambient temperature to give rGO-g-PAA/PAM hydrogels. The interfacial interaction between GO/rGO and hydrogel matrix was improved by reversible hydrogen bonds between the grafted PAA chains and PAM matrix. Consequently, both GO-g-PAA/PAM and rGO-g-PAA/PAM hydrogels exhibited improved tensile properties, excellent energy dissipation, and rapid self-recovery. The in situ chemical reduction of GO-g-PAA in hydrogel matrix endowed rGO-g-PAA/PAM hydrogels with satisfactory electrical conductivity and obvious resistance change upon stretching. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48781.