Improving the metal ion release from nanoparticles embedded in a polypropylene matrix for antimicrobial applications

Novel antimicrobial materials can be produced by adding copper nanoparticles (CNPs) into a polymeric matrix. To improve the behavior of these systems, the effect of different variables on the dispersion of copper metal nanoparticles embedded in a polypropylene matrix by melt mixing and its ion release was analyzed. The variables studied were predispersion of particles in liquid solvents, polymer molecular weight, melt mixing conditions, addition of a compatibilizer agent, two‐step melt mixing, and surface functionalization of the metal particles. Our results show that by modifying these variables, a significant improvement in the filler dispersion, as quantified by optical microscope, can be obtained. For instance, the original CNP agglomerates can be reduced from an average size of 70 µm to a final average size of 30 µm and a larger amount of nanometric agglomerates by using a compatibilizer or predispersed nanoparticles. Moreover, by using surface‐functionalized CNPs, micrometric agglomerates were not observed. Noteworthy, there is a direct relationship between the filler dispersion and the release of biocide copper ions when improvements were larger than a certain threshold with increases as high as 40%. These findings can be used in the development of antimicrobial materials with tailored behavior. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41232.     

Magnetic nanoparticles embedded in pectin‐based hydrogel for the sustained release of diclofenac sodium

A supermagnetic polysaccharide‐based nanocomposite gel has been developed as a potential drug delivery system. The gel was made via graft copolymerization of 2‐acrylamido‐2‐methylpropanesulfonic acid on pectin using ammonium peroxodisulfate as an initiator and N,N‐methylenebisacrylamide as a crosslinker under microwave irradiation. The magnetic nanoparticles (MNPs) were incorporated within the gel network via an in situ method of diffusion of Fe²⁺/Fe³⁺ followed by reduction with ammonia solution. The graft copolymer gel and its nanocomposite were characterized using attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, powder X‐ray diffraction, field‐emission scanning electron microscopy, energy‐dispersive X‐ray spectroscopy and transmission electron microscopy. The magnetic properties of the nanocomposite were measured using a vibrating sample magnetometer and mechanical properties using a tensile compressive tester. The gel was evaluated for adsorption and release of the drug diclofenac sodium. The presence of MNPs is observed to enhance significantly the mechanical properties, swelling capacity, drug loading and release ability of the graft polymer gel. The increased porosity of the gel network and higher surface area of MNPs allowed for 20% higher adsorption of diclofenac sodium molecules compared to the parent nonmagnetic gel. About 95% of the loaded drug was released from the MNP‐containing gel. The drug release pattern followed first‐order kinetic model and the Higuchi square root model, indicating swelling‐controlled diffusion to be the mode of drug release. © 2018 Society of Chemical Industry     

Sustained release of iodine from a polymeric hydrogel device for water disinfection

2‐Hydroxyethyl methacrylate (HEMA) based polymeric hydrogels were synthesized by free‐radical redox bulk polymerization technique using 1% ethyleneglycol dimethacrylate (EGDMA) as crosslinking monomer and ammonium persulfate (APS) and N,N,N′,N′‐tetramethyl ethylenediamine (TEMED) as redox initiator. Polymeric hydrogel samples were loaded with solid elemental iodine. Thermal and physical characteristics of polymer before loading and after 3 months release of iodine were evaluated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). On immersing in water, different forms of iodine were released from the hydrogel device. The amount and rate of release of I^? and I were measured by analytical techniques. Released iodine species showed broad spectrum antimicrobial properties and release was sustained for about 120 days. Polymeric hydrogel iodine‐based system developed can be used as a device for controlled release of iodine species at concentration levels sufficient for disinfection to get potable water. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3334–3340, 2007     

Silver nanoparticles embedded gum ghatti-graft-poly(N,N-dimethylacrylamide) biodegradable hydrogel: evaluation as matrix for controlled release of 2,4-dichlorophenoxyacetic acid

The present work explores the use of a nanocomposite hydrogel made using Gum ghatti (Gg), N,N-dimethylacrylamide (DMA) and N,N- methylene- bis-acrylamide (MBA) as a matrix for controlled release of 2,4-dichlorophenoxy acetic acid (2,4-D). Stable and uniformally distributed silver nanoparticles (Ag NP) were formed by the reduction of AgNO₃ using TCS within the gel network. The Gg-g-PDMA and Ag NPs entrapped gel (Gg-g-PDMA-SN) were characterized by FT-IR, XRD, TGA, SEM, EDS and TEM techniques. The presence of Ag NPs is observed to enhance the swelling ability and the release efficiency of the Gg-g-PDMA gels significantly and also showed higher biodegradability. The gels exhibited prolonged release of the 2,4-D indicating good potential to be used as matrix for controlled release applications in agriculture.     

Controlled release of drugs from hydrogel matrices

A series of polymers with wide ranges of water absorptivity were prepared and utilized as matrices for the controlled release of drugs. The drugs were introduced into the matrices by use of an appropriate organic solvent. Release rates of erythromycin and erythromycin estolate from hydrogel were analyzed kinetically and found to conform to Higuchi's equation, that is, M_t = A(2DtC_sC₀)^1/2, where M_t is the accumulated amount of released drug at time t, A is the surface area, D is the diffusion coefficient, C_s is the solubility of drug in the hydrogel matrix, and C_o is the initial drug content of the preparation in the swollen state. The relationship between the water content of hydrogel and the diffusion coefficient of erythromycin in hydrogel is expressed by the equation D = 3.03 × 10^?10 W^3.03 (cm²/sec), where W is the water content (%). The release rate of drug can be controlled quantitatively by adjustment of the water content of the hydrogel matrix. A guide to the design for the preparation is suggested.     

Modeling the controlled release of drug embedded in a plate-like polymer matrix

The controlled release of over-loaded drug in a plate-like polymer matrix, the Higuchi's problem, is investigated theoretically. Taking the advantage of Landau transformation, we restore the concentration profile of drug in a polymer matrix, the rate of release of drug from the polymer matrix, and the temporal variation of location of the moving boundary taking the external mass transfer resistance into account. The applicability of the series of moving boundaries, a numerical approach often adopted, is examined. We found that it may become ineffective when the over-loading of drug in a polymer matrix is too small. In contrast, our method has no such limitation. We conclude that assuming the transfer of drug to occur at a pseudo-steady-state condition is inadequate if the degree of over-loading for drug is low or the external mass transfer resistance is significant.     

Ion beam-induced shaping of Ni nanoparticles embedded in a silica matrix: from spherical to prolate shape

Present work reports the elongation of spherical Ni nanoparticles (NPs) parallel to each other, due to bombardment with 120 MeV Au⁺⁹ ions at a fluence of 5 × 10¹³ ions/cm². The Ni NPs embedded in silica matrix have been prepared by atom beam sputtering technique and subsequent annealing. The elongation of Ni NPs due to interaction with Au⁺⁹ ions as investigated by cross-sectional transmission electron microscopy (TEM) shows a strong dependence on initial Ni particle size and is explained on the basis of thermal spike model. Irradiation induces a change from single crystalline nature of spherical particles to polycrystalline nature of elongated particles. Magnetization measurements indicate that changes in coercivity (H _c) and remanence ratio (M _r/M _s) are stronger in the ion beam direction due to the preferential easy axis of elongated particles in the beam direction.     

Sustained release of dexamethasone from drug‐loading PLGA scaffolds with specific pore structure fabricated by supercritical CO2 foaming

Inducing differentiation of bone marrow stem cells to generate new bone tissue is highly desirable by controlling the release of some osteoinductive or osteoconductive factors from porous scaffolds. In this study, dexamethasone was selected as a representative of small molecule drugs and dexamethasone‐loading porous poly(lactide‐co‐glycolide) (PLGA) scaffolds were successfully fabricated by supercritical CO₂ foaming. Scanning electron microscopy images showed that scaffolds had rough and relatively interconnected pores facilitating cells adhesion and growth. Specially, dexamethasone which was incorporated into PLGA matrix in a molecularly dispersed state could serve as a nucleation agent to be helpful for the formation of interconnected pores. Dexamethasone‐loading porous PLGA scaffolds exhibited sustained release profile, and the delivery of dexamethasone from porous scaffolds could last for up to 2 months. The cumulative released amount of dexamethasone was relevant with drug loading capacity (1.66%–2.95%) and pore structure of scaffolds; while the release behavior was anomalous (non‐Fickian) transport by fitting with the simple exponential equation, which had a diffusional exponent n higher than 0.5. It is feasible to fabricate drug‐loading porous scaffolds by supercritical CO₂ foaming with specific pore structure and sustained release profile, which can be well applied in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46207.     

Optimization of protein encapsulation in PLGA nanoparticles

Influences of process parameters were investigated on the efficiency of encapsulation of bovine serum albumin (BSA) in poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles produced by w₁/o/w₂ (water-in-oil-in-water) double emulsion-solvent evaporation method. According to a 5-factorial 3-level Box-Behnken type experimental design aqueous solution of BSA was emulsified in an immiscible organic phase composed of dichloromethane and various quantities of dissolved PLGA to get water-in-oil (w₁/o) emulsion. This latter was then dispersed in a second aqueous phase (w₂) containing poly-vinyl-alcohol (PVA) surfactant as an emulsifier/stabilising agent. PLGA nanoparticles with encapsulated BSA were obtained by evaporating the dichloromethane from the w₁/o droplets. Encapsulation efficiency was determined as the weight ratio of BSA remained in the PLGA nanoparticles relative to the total weight of BSA used in the process. By statistical evaluation of the experimental results an equation was proposed to predict the encapsulation efficiency as a function of five process variables. Two optimization procedures were carried out to increase the efficiency of encapsulation, with and without constraints referring to the required mean particle size. Correlation was found between the latter and the achievable maximal encapsulation efficiency under optimal process conditions.     

Sustained release of potassium diclofenac from a pH‐responsive hydrogel based on gum arabic conjugates into simulated intestinal fluid

This work describes the preparation, the swelling properties and the potassium diclofenac (KDF) release profile of hydrogels of gum arabic (GA), N′,N′‐dimethylacrylamide, and methacrylic acid. In order to convert GA into a hydrogel, the polysaccharide was vinyl‐modified with glycidyl methacrylate. The hydrogels showed pH‐responsive swelling changes, which were more expressive in the basic environment. Release data of KDF were adjusted to a diffusion‐based kinetic model that provides an important insight on affinity of the drug for hydrogel and solvent, which may be the leading parameter for release of guest molecules from polymers. The KDF release from the hydrogels into simulated intestinal fluid decreases when the amount of modified GA increases. This was demonstrated to be due to the higher affinity of KDF for GA‐richer hydrogel, which makes the anti‐inflammatory release less favorable. The analysis of released drug half‐time (t_1/2 = 16.10 and 21.51 h) indicated sustained release characteristics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43319.     

Functional chemical modification of a porcine acellular dermal matrix with a modified naturally derived polysaccharide crosslinker

Antibacterial and physicochemical properties are generally considered important features of the porcine acellular dermal matrix (pADM). Oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was applied to crosslink with pADM at dosages of 1, 2, 4, 8, and 16%. The properties of the crosslinked pADM (OHTCC-pADM) were evaluated. DSC and TG analysis suggested that crosslinking could promote the thermal stability, the highest T_d, and T_max of OHTCC-pADM (8%) was 80 °C and 325 °C, which has been improved by 15 °C and 13 °C, respectively. While FTIR and AFM tests indicated that the structure integrity of collagen could still be maintained. SEM tests demonstrated the sustained three-dimensional architecture of OHTCC-pADM with appropriate porosity. Moreover, OHTCC-pADM exhibited improved ability to resist collagenase degradation, the degradation rate of 4%-, 8%-OHTCC-pADM was <50%. The tensile strength of OHTCC-pADM proved to be superior compared to pADM. Furthermore, 8%-OHTCC-pADM exhibited nearly 90% antibacterial activity against Escherichia coli, and Staphylococcus aureus. In addition, the results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide study showed that the cytocompatibility of OHTCC-pADM decreased with the increasing the amount of OHTCC, but all relative proliferation rates were above 80%. In conclusion, our study revealed that OHTCC stabilized and functionalized pADM while preserving good cytocompatibility. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47633.     

A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release kinetics and biological activity

In the present article a facile synthesis of cerium oxide nanoparticles (CNPs) encapsulated in PLGA microparticles is reported. The release kinetics of the CNPs from the PLGA matrix was investigated under acidic, basic and near-neutral pH. A diffusion model was applied to determine the diffusivity of the CNPs from the PLGA matrix. The morphology of the degraded PLGA particles was characterized by high resolution SEM. Superoxide dismutase (SOD) mimetic activity was retained in released CNPs for a longer period of time (～90 days) under different pH. PLGA encapsulated CNP showed excellent biocompatibility. This study demonstrates a potential strategy to deliver CNPs using biodegradable PLGA that ensures a slow release of the CNPs over a long period of time. Thus, the synthesized PLGA encapsulated CNPs could find potential applications in tissue engineering like bone remodelling and regeneration, and protection from disorders caused by neurodegeneration.     

In situ incorporation of monodisperse drug nanoparticles into hydrogel scaffolds for hydrophobic drug release

The effective and locally sustained delivery of hydrophobic drug with hydrogels as carriers is still a challenge owing to the inherent incompatibility of hydrophilic hydrogel network and hydrophobic drug. One promising approach is to use porous hydrogels to encapsulate and deliver hydrophobic drug in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated hydrophobic drug nanoparticles into the hydrogels because of the severe nanoparticle aggregation during the loading process. In this article, we firstly designed and fabricated efficient drug nanoparticles embedded hydrogels for hydrophobic drug delivery by incorporating monodisperse silybin (hydrophobic drug for liver protection) nanoparticles into acrylated hyaluronic acid (HA‐AC) based hydrogels through in situ cross‐linking. The silybin nanoparticles embedded hydrogel scaffolds proved to be a good sustained release system with a long period of 36 h. The drug release from this hybrid hydrogels could be modulated by tuning HA‐AC concentration, cross‐linking ratio, chain length of cross‐linker and drug loading amount. The different kinetic models were applied, and it was observed that the release profile of silybin best followed the Hixson‐Crowell model for the release of drug from the hydrogels embedding silybin nanoparticles. It could be envisioned that this process would significantly advance the potential applications of hydrogel scaffolds mediated hydrophobic drug delivery in clinical therapies. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43111.     

Synthesis and encapsulation of magnetite nanoparticles in PLGA: effect of amount of PLGA on characteristics of encapsulated nanoparticles

Oleic acid-coated superparamagnetic iron oxide nanoparticles (Fe₃O₄) encapsulated within poly(d,l-lactide-co-glycolide) (PLGA) particles were prepared by the w/o/w emulsion technique using poly(vinyl alcohol) as a dispersant. The concentration of PLGA in the oil phase was varied (5, 15, 30, 45, and 60?mg/ml) at constant magnetite concentration in the oil phase (5?mg/ml) to study the properties of composite Fe₃O₄–PLGA nanoparticles. Even though PLGA concentration varied widely in the oil phase, the weight percent of 7–16?nm diameter magnetite in the particles varied only from 56 to 62?% (23–28?vol.%). The obtained composite nanoparticles were essentially spherical with magnetite spatially uniformly dispersed in individual PLGA particles, as measured by transmission electron microscopy (TEM). Also, the magnetite concentration in each particle did not vary widely as determined qualitatively via microscopy. Hydrodynamic diameters of the composite nanoparticles as measured by dynamic light scattering increased by approximately 10?% with added magnetite, with a smaller relative increase in diameter measured by TEM. The zeta potential of the particles was about ?26?mV, independent of Fe₃O₄ loading. Relatively high saturation magnetizations (36–45?emu/g) were measured for these highly loaded particles, with the latter value only 7?emu/g lower than the value measured for the oleic acid-coated particles alone.     

硅基纳米材料用于阿司匹林长效缓释的研究

表面活性剂采用十六烷基三甲基溴化铵为活性成分,硅源采用正硅酸乙酯,利用低温水热法合成了MCM-4l介孔分子筛,采用动态吸附法将阿司匹林药物吸附到分子筛MCM-41的孔道中,吸附前后的介孔分子筛分别利用傅里叶红外光谱(IR)、紫外光谱(UV)、X射线衍射仪(XRD)、扫描电子显微镜(SEM)等对吸附前后的分子筛进行了表征;借助紫外-可见吸收光谱(UV)研究了分子筛的最大吸附量、吸附时间、体外释放等。结果显示,所合成的分子筛MCM-41有序的介孔材料;MCM-4l用于药物阿司匹林的载体最大载药量为:45mg·g-1(m(药物)/m(载体))和良好的缓释效果。     

Anisotropy investigation of cobalt ferrite nanoparticles embedded in polyvinyl alcohol matrix: A Monte Carlo study

The magnetic properties of the cobalt ferrite/polyvinyl alcohol nanocomposites have been studied experimentally and theoretically. For investigation the impact of polymeric matrix on magnetic properties of magnetic nanoparticles, four different processes have been considered for synthesizing the polymer based nanocomposites by co-precipitation method. The effective magnetic anisotropy obtained by Monte Carlo simulation and law of approach to the saturation magnetization showed a significant decrease relative to the bulk and bare cobalt ferrite nanoparticles. The polymeric matrix interacted with the surface of particles by different strength and made them approximately non-interacting. The as synthesized samples characterized by X-Ray diffractions (XRD) and Fourier transform infrared spectroscopy (FT-IR). Magnetic measurements were carried out at room temperature using a vibrating sample magnetometer (VSM).     

Sustained release of tetracycline from polymeric periodontal inserts prepared by extrusion

The specific aim of this study was to prepare polymeric inserts containing tetracycline that are intended for intraperiodontal pocket application. The inserts were prepared by a simple extrusion method and based on mixtures of polyvinyl alcohol, glyceryl behenate, xanthan gum, carrageenan, hydroxypropyl methylcellulose, and hyaluronic acid in addition to tetracycline HCL. The inserts were characterized regarding average weight, diameter, water content, and average tetracycline content. Zero‐order release kinetics of tetracycline were observed in case of three of the four batches of the prepared inserts with release profiles that were essentially similar. The release of the drug was incomplete in all cases. This was due, as shown by the equilibrium dialysis tests, to tetracycline binding by the polymers. However, the inserts performed more than 7 days drug sustained release which indicates promising results for local delivery of tetracycline for treatment of periodontal disease. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Controlled release of prednisolone acetate from molecularly imprinted hydrogel contact lenses

The aim of this work was to study the influence of methacrylic acid (MAA) as a comonomer and the application of a molecular imprinting technique on the loading and release properties of weakly crosslinked 2‐hydroxyethyl methacrylate (HEMA) hydrogels, with a view toward their use as reloadable soft contact lenses for the administration of prednisolone acetate (PA). The hydrogels were prepared with HEMA (95.90–98.30 mol %) as a backbone monomer, ethylene glycol dimethacrylate (140 mM) as a crosslinker, and MAA (0, 50, 100, or 200 mM) as a functional monomer. Different PA/MAA molar ratios (0, 1 : 8, 1 : 6, and 1 : 4) in the feed composition of the hydrogels were also applied to study the influence of the molecular imprinting technique on their binding properties. The hydrogels (0.4 mm thick) were synthesized by thermal polymerization at 60°C for 24 h in a polypropylene mold. The hydrogels were then characterized by the determination of their swelling and binding properties in water. Their loading and release properties were also studied in 0.9% NaCl and artificial lachrymal fluid. Increasing the MAA content of the hydrogel and applying the molecular imprinting technique led to an increase in the loading capacity of the hydrogel. The optimized imprinted hydrogel showed the highest affinity for PA and the greatest ability to control the release process, sustaining it for 48 h. The results obtained clearly indicate that the incorporation of MAA as a comonomer increased the PA loading capacity of hydrogel. Our data showed that the molecular imprinting technique also had a significant effect on the loading and release properties of the hydrogels. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

缓释材料用量对水溶性药物骨架片释放度的影响

水溶性药物卡托普利（Captopril,Cap）是第一代血管紧张素转换酶抑制剂,是治疗高血压的首选药物之一．常用剂型为糖衣片或普通片,由于其生物半衰期短,需要Ft服三次,且峰谷浓度差别较大,这可能是引起肺淤血、眩晕、头疼、肠胃道紊乱等不良反应的原因,有必要将其制为缓释剂型．国外已有Cap缓释胶囊上市,由于水溶性药物本身溶出很快,其释放较难被阻滞,国内尚无Cap的缓释品种上市．本实验参考国内外Cap缓释制剂的处方和制备工艺,筛选研制了Cap缓释骨架片．     

Towards a better understanding of the release mechanisms of caffeine from PLGA microparticles

Poly(lactic-co-glycolic acid) (PLGA)-based microparticles can be successfully used to control the release rate of a drug and optimize the therapeutic efficacy of a medical treatment. However, the underlying drug release mechanisms can be complex and are often not fully understood. This renders system optimization cumbersome. In this study, differently sized caffeine-loaded PLGA microparticles were prepared and the swelling and drug release behaviors of single microparticles were monitored upon exposure to phosphate buffer pH 7.4. Ensembles of microparticles were characterized by X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, gel permeation chromatography, and optical microscopy. The observed triphasic drug release patterns could be explained as follows. The initial burst release can be attributed to the dissolution of tiny drug crystals with direct surface access. The subsequent second drug release phase (with an about constant release rate) could be attributed to the release of drug crystals in regions, which undergo local swelling. The third release phase (again rapid, leading to complete drug exhaust) could be explained by substantial polymer swelling throughout the systems. Once a critical polymer molecular weight is reached, the PLGA chains are sufficiently hydrophilic, insufficiently entangled and the osmotic pressure created by water soluble degradation products attracts high amounts of water into the system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48710.