Preparation and Cytotoxicity of Poly(Methyl Methacrylate) Nanoparticles for Drug Encapsulation

Summary: This work aimed to produce poly(methyl methacrylate) nanoparticles for use in drug encapsulation. The polymer nanoparticles were produced using miniemulsion polymerization technique. Monomer miniemulsion showed moderate stability and polymer average particle size was about 90 nm. PMMA nanoparticles were tested for toxicity in human leukemic cell strain K562 and they did not show any adverse effect on cell viability. Therefore, poly(methyl methacrylate) nanoparticles are suitable to encapsulate antitumor agents.     

Compatibilization of the PBA/PMMA core/shell latex interphase. I. Effect of PMMA macromonomer

In this work poly(methyl methacrylate) (PMMA) macromonomer is used as a compatibilizing agent in a poly(butyl acrylate) (PBA)/PMMA core/shell latex system. The incorporation of the PMMA macromonomer was achieved by copolymerizing it with BA monomer using miniemulsion polymerization. PBA seed latex was also synthesized without the macromonomer present to compare the compatibilizing effects with the PMMA macromonomer. The second stage methyl methacrylate monomer was added semi-continuously to the PBA seed latexes under monomer-starved conditions. Solid-state ¹³C-NMR [H]T₁ρ relaxation studies were used to determine the effect of PMMA compatibilizer on these PBA/PMMA core/shell latex interphase regions. The thickness of the interphase of the core/shell particles prepared with and without the PMMA macromonomer compatibilizing agent are calculated to be in the range of 15–16 nm and 10–12 nm, respectively. Electron microscopy revealed that the seed latex prepared with the PMMA macromonomer achieved a more uniform coverage with the second stage PMMA polymer as compared to the latex synthesized without the compatibilizing agent present. It is concluded that the PMMA macromonomer is effective in increasing the thickness of the interphase region and also the amount of interfacial PMMA. © 1996 John Wiley & Sons, Inc.     

Morphology of PU/PMMA hybrid particles from miniemulsion polymerization: Thermodynamic considerations

The morphology of PU/PMMA hybrid particles prepared by miniemulsion polymerization was predicted through the consideration of their Gibbs free energy changes. Five morphological states of PU/PMMA hybrid particles were proposed and their Gibbs free energy changes were calculated. Before the formation of hybrid particles, the initial state included a monomer mixture of PU prepolymer, MMA, a chain extender, TMP, and an initiator, which was in droplets suspended in water containing SDS. Two assumptions were made. First, the densities of all states were the same. Secondly, secondary nucleation of particles was negligible. Thus the size of initial droplet and final particle was unchanged through miniemulsion polymerization. The interfacial tensions were measured by a pendant drop method and were used for calculation. The preferred morphology of PU/PMMA hybrid particle had the minimum value of ΔG_phase. Different NCO/OH ratios of PU and initiators of MMA were used to study the morphological change of PU/PMMA hybrid particles. When BD was used as the chain extender of PU, the hybrid particles showed the PU‐rich phase as the shell and PMMA‐rich as the core. When incorporating bisphenol A into PU polymer, the homogeneous structure of hybrid particle was preferred. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3359–3369, 2007     

RAFT Miniemulsion Polymerization of MMA with Cumyl Dithiobenzoate as Chain Transfer Agent

As a kind of living free radical polymerizations, reversible addition-fragmentation chain transfer (RAFT) has been proved to be an important technique nowadays as it is applicable to a wide range of monomers at a wide range of temperature below 100oC. In …     

Preparation of magnetic polymer colloids with Brownian magnetic relaxation

Magnetic polymer colloids (MPCs) consisting of CoFe₂O₄ nanoparticles (NPs) embedded in a poly(methyl methacrylate) (PMMA) matrix were synthesized by magnetic miniemulsion polymerization. CoFe₂O₄ NPs were modified with 3-trimethoxysilylpropylmethacrylate and directly emulsified with different concentrations of sodium dodecyl sulfate under ultrasonication for subsequent miniemulsion polymerization. The average diameter of the CoFe₂O₄/PMMA spheres (about 200 nm) was controlled by varying the amount of surfactant. Thermogravimetric analysis indicated that the magnetic content was in the range of 44 to 73 %. Magnetic properties of the dispersions were investigated by measuring equilibrium magnetization curves and the dynamic magnetic susceptibility as a function of frequency. The MPCs were found to follow the Debye model for the dynamic magnetic susceptibility, with a characteristic time given by the rotational hydrodynamic resistance and thermal energy through the Stokes-Einstein relation. This demonstrates that the MPCs respond to applied magnetic fields by rotating. Due to their uniform size and high magnetic loading, these colloids may be suitable in a variety of applications, including nanoscale mechanical probes and actuators in complex fluids and biological systems.     

β-CD存在下MMA细乳液体系的RAFT聚合

近年来，活性自由基聚合已成为高分子合成领域中的一个热门课题．Rizzardo研究小组提出了一种新型活性自由基聚合反应，即RAFT(Reversible addition-fragmentation chain transfer)聚合．RAFT反应在传统的自由基聚合中加入了具有高链转移常数和特定结构的链转移剂——双硫酯类化合物．当链转移剂的浓度足够大时，链转移反应由不可逆变为可逆，聚合反应也随之发生质的变化，由不可控     

RAFT-细乳液法合成PMMA-b-PGMA两嵌段共聚物

以甲基丙烯酸甲酯(MMA)为单体,S-正十二烷基-S′-(α,α′-二甲基-α″-乙酸基)三硫代碳酸酯为链转移剂,经RAFT/细乳液法制得PMMA(PDI 1.44)。以PMMA细乳液为种子乳液,与甲基丙烯酸缩水甘油酯聚合合成了PMMA-b-PGMA两嵌段聚合物(1),其结构和性能经¹H NMR, FT-IR, GPC和DSC确证。结果表明：1的PDI为2.04,玻璃化转变温度为92.35 ℃。     

Statistical design strategies to optimize properties in miniemulsion polymerization of methyl methacrylate

PMMA particles were synthesized by a miniemulsion polymerization method using hexadecane as costabilizer and sodium dodecyl sulfate as surfactant. Full factorial experimental design incorporating the linear regression analysis of the experimental values was used to illustrate the usefulness of this technique in miniemulsion polymerization studies. The effect of initiator concentration, costabilizer concentration, surfactant concentration, sonication time and amplitude, and their interactions on the particle size were identified. Costabilizer and surfactant concentrations influence both particle size individually whereas initiator concentration influences particle size via its interactions with the costabilizer and the surfactant. Sonication parameters influence also greatly the particle size. Two mathematical models were established, and have demonstrated the capability of predicting particle diameter from the synthesis conditions with a precision of 1-2 nm over a range from 75 to 180 nm.     

Synthesis of PMMA‐b‐PBA block copolymer in homogeneous and miniemulsion systems by DPE controlled radical polymerization

In this research, poly(methyl methacrylate)‐b‐poly(butyl acrylate) (PMMA‐b‐PBA) block copolymers were prepared by 1,1‐diphenylethene (DPE) controlled radical polymerization in homogeneous and miniemulsion systems. First, monomer methyl methacrylate (MMA), initiator 2,2′‐azobisisobutyronitrile (AIBN) and a control agent DPE were bulk polymerized to form the DPE‐containing PMMA macroinitiator. Then the DPE‐containing PMMA was heated in the presence of a second monomer BA, the block copolymer was synthesized successfully. The effects of solvent and polymerization methods (homogeneous polymerization or miniemulsion polymerization) on the reaction rate, controlled living character, molecular weight (M_n) and molecular weight distribution (PDI) of polymers throughout the polymerization were studied and discussed. The results showed that, increasing the amounts of solvent reduced the reaction rate and viscosity of the polymerization system. It allowed more activation–deactivation cycles to occur at a given conversion thus better controlled living character and narrower molecular weight distribution of polymers were demonstrated throughout the polymerization. Furthermore, the polymerization carried out in miniemulsion system exhibited higher reaction rate and better controlled living character than those in homogeneous system. It was attributed to the compartmentalization of growing radicals and the enhanced deactivation reaction of DPE controlled radical polymerization in miniemulsified droplets. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4435–4445, 2009     

Synthesis of a photoactive gemini surfactant and its use in AGET ATRP miniemulsion polymerisation and UV curing

A novel photoactive gemini surfactant was easily synthesised in high yields. The multi-functional molecule can be used as a gemini surfactant, a benzophenone type photoinitiator, and as an ATRP initiator. Poly(methyl methacrylate) (PMMA) and poly(methyl methacrylate)-block-poly(allyl methacrylate) (PMMA-b-PAMA) were prepared using the photoactive gemini surfactant as an ATRP initiator under soap-free miniemulsion polymerisation conditions. Kinetic results of the miniemulsion polymerisation of methyl methacrylate (MMA) indicate that the reaction has controlled/living characteristics. UV curing was performed by irradiation of the linear PMMA-b-PAMA polymer, in which PMMA-b-PAMA containing a benzophenone moiety functioned as a macromolecular photoinitiator.     

Polymeric Nanocapsules Containing Nematic LCs as Hydrophobes in Miniemulsion Polymerization

The distinct polymeric nanocapsule hybrid‐structures consisting of LCs in the core and PMMA or polystyrene in the corona domain were prepared by one‐step miniemulsion polymerization. Nematic LCs (4′‐pentyl‐4‐biphenylcarbonitrile and 4′‐heptyloxy‐4‐biphenylcarbonitrile) were especially adopted as hydrophobes that can suppress Ostwald ripening and had an important role to stabilize the miniemulsion droplets and control the size distributions of the latexes. The polymeric nanocapsule structures with narrow size distributions were confirmed by TEM and DLS measurements.

     

Competitive Cellular Uptake of Nanoparticles Made From Polystyrene,Poly(methyl methacrylate), and Polylactide

The uptake behavior of negatively charged fluorescent nanoparticles made from different polymers (PS, PMMA, and PLLA) is studied on HeLa cells. All particles are obtained by the miniemulsion process using sodium dodecylsulfate as anionic surfactant. The size of the particles is in the range 105–125 nm. Cell uptake is analyzed by flow cytometry and reveals a higher uptake of PLLA particles compared to PMMA and PS particles. In competitive uptake studies two different types of particles are co‐incubated with the HeLa cells; the results indicate a mutual influence of the particles on their uptake behavior. A reduced internalization of PLLA particles in the presence of PS particles is observed, although neither the co‐incubation of PMMA and PLLA nor of PMMA and PS shows similar effect.

     

Mathematical modeling of seeded miniemulsion copolymerization for oil-soluble initiator

A mathematical model of seeded miniemulsion copolymerization of styrene-methyl methacrylate for oil-soluble initiator is presented. The mathematical model includes the mass transfer, from the miniemulsion droplets to the polymer particles, by both molecular diffusion and collision between miniemulsion droplets and the polymer particles. The mathematical model also includes the calculation of both the distribution of partices with i radicals and the average number of radicals per particle in the miniemulsion copolymerization using oil-soluble initator. Studies were carried out on the mass transfer coefficients of monomers across the interface between the miniemulsion droplet and the aqueous phase, hexadecane concentration in the miniemulsion droplets, the miniemulsion droplet sizes, and the collision between miniemulsion droplets. The results indicated that the copolymerization of styrene-methyl methacrylate was not a mass transfer controlled process. The mass transfer by collision between miniemulsion droplets and polymer particles plays an important role and was included in the model in order to predict the experimental data of seeded miniemulsion copolymerization.     

The role of surfactant in controlling particle size and stability in the miniemulsion polymerization of polymeric nanocapsules

The influence of surfactant concentration on particle size and stability of nanocapsules with liquid cores, synthesized by an in situ miniemulsion polymerization process, was investigated. Although the role of surfactant in the synthesis of particles in the nanometer range has frequently been documented, the transition to structured particles, which almost consist of a 1:1 weight ratio of encapsulated liquid hydrophobe to polymeric shell, has not received much attention. Capillary hydrodynamic fractionation (CHDF) analyses were used to evaluate particle size. Results were subsequently used to stoichiometrically calculate the area which is occupied per surfactant molecule on the particle surface. These results were compared with “classical” miniemulsion data, i.e. data generated from the synthesis of polymeric latexes in the presence of a hydrophobe, but at a much lower hydrophobe:monomer ratio as was used here. The surface coverage per surfactant molecule could be related to the surface tension of the latex, thus providing a relationship between particle size and stability. CHDF was furthermore used to investigate particle size after grafting of a secondary PMMA shell. Data obtained from CHDF experiments were in all cases confirmed by TEM analysis of the synthesized particles. To conclude, the synthesis of nanocapsules with liquid cores could be successfully scaled-up, with retention of all the characteristics of the final latex.     

Study of Polymer-Cement Composite Containing Portland Cement and Aqueous Poly (methyl methacrylate) Latex Polymer by Fourier-Transform Infrared (FT-IR) Spectroscopy

The polymer-cement composite is an immiscible band having modified morphology. Polymer phase improves the toughness of brittle cement and has a reinforcing effect, and interactions between cement components and polymers provide stability. In this study, polymer latex [poly(methyl methacrylate), PMMA] – cement paste was prepared with different weight proportions of polymer content. The main scientific objective of this report has been the analysis and the prediction of high strength with the aim of understanding the interactions of PMMA polymer with Portland cement after hydration reaction of cement pastes and curing the specimens for 28 days. The samples were studied by Fourier transform infrared (FT-IR) spectroscopy. The results are critically examined. It is shown that bands support the interaction of PMMA with cement in the composite.     

Block copolymers of dodecafluoroheptyl methacrylate and butyl methacrylate by RAFT miniemulsion polymerization

Reversible addition‐fragmentation chain transfer (RAFT) miniemulsion polymerization of butyl methacrylate (BMA) and dodecafluoroheptyl methacrylate (DFMA) was carried out with 2‐cyanoprop‐2‐yl dithiobenzoate (CPDB) as chain transfer agent (CTA). Concentration effects of RAFT agent and initiator on kinetics and molecular weight were investigated. No obvious red oil layer (phase's separation) and coagulation was observed in the first stage of homopolymerization of BMA. The polymer molecular weights increased linearly with the monomer conversion with polydispersities lower than 1.2. At 75 °C, the monomer conversion could achieve above 96% in 3 h with [momomer]:[RAFT]:[KPS] = 620:4:1 (mole ratio). The results showed excellent controlled/living polymerization characteristics and a very fast polymerization rate. Furthermore, the synthesis of poly(BMA‐b‐DFMA) diblock copolymers with a regular structure (PDI < 1.30, PMMA calibration) was performed by adding the monomer of DFMA at the end of the RAFT miniemulsion polymerization of BMA. The success of diblock copolymerization was showed by the molecular weight curves shifting toward higher molar mass, recorded by gel permeation chromatography before and after block copolymerization. Compositions of block copolymers were further confirmed by ¹H NMR, FTIR, and DSC analysis. The copolymers exhibited a phase‐separated morphology and possessed distinct glass transition temperatures associated with fluoropolymer PDFMA and PBMA domains. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1585–1594, 2007     

The synthesis of diene – alkyl methacrylate diblock and heteroarm star copolymers

The synthesis of A₂B₂ heteroarm stars, where A is either polyisoprene (PI) or polybutadiene (PB) and B is either poly(methyl methacrylate) (PMMA) or poly(butyl methacrylate) (PBMA) has been achieved using living anionic polymerization. Following polymerization of the diene in hexane by sec‐BuLi, the solvent was changed to THF and the living chains were linked in pairs – without loss of anionic reactivity – using 1,2‐bis[4‐(1‐phenylethenyl)]ethane (EPEB). Star synthesis was completed by the addition of MMA or BMA monomer at −78°C. The diblocks were prepared by sequential polymerization. The resulting stereochemistries were those of greatest interest from a practical standpoint, i.e., PI or PB with a high 1,4‐content (which is highly elastic) and syndiotactic PMMA (which has a high T_g).     

Miniemulsion polymerization of styrene with chain transfer agent as cosurfactant

Miniemulsion polymerization of styrene with the chain transfer agent n-dodecyl mercaptan (DDM) used as cosurfactant was studied. Droplet size and shelf life for unpolymerized miniemulsions were measured and compared with those of equivalent macroemulsions. The miniemulsion monomer droplets with dodecyl mercaptan as cosurfactant were very stable. Shelf lives were from 17 h to 3 months. The kinetics of miniemulsion polymerization were studied. Unlike other miniemulsion systems where the cosurfactant does not act as a chain transfer agent, the polymerization rate falls with cosurfactant level because the chain transfer agent enhances radical desorption from the particles. The polymerization rate in all the miniemulsions was lower than that of the corresponding macroemulsions. Polymerized particles were larger than in the corresponding macroemulsions, but molecular weights were lower. Results indicate that DDM can serve as an effective cosurfactant as well as a chain transfer agent. The fact that the molecular weights are lower in the miniemulsion reactions indicates predominant droplet nucleation. © 1997 John Wiley & Sons, Inc.     

Polystyrene nanoparticles doped with a luminescent europium complex

Polystyrene nanoparticles doped with a luminescent europium complex, Eu(tta)(3)phen, are prepared by miniemulsion polymerization. The influence of the complex on the miniemulsion polymerization is investigated by the systematic variation of the initial concentration of Eu(tta)(3)phen from 2 to 7 wt% relatively to styrene. A maximum doping level of about 2% by weight in the final particles can be achieved. At higher doping levels, destabilization of the miniemulsion leads to a loss of reproducibility with respect to both the degree of conversion and the final Eu content of the particles. Doped nanoparticles of varying diameter, ranging from 19 to 94 nm, are successfully prepared. Steady-state and time-resolved luminescence measurements indicate that the luminescence properties of Eu(tta)(3)phen in the doped latexes are unchanged from those found in THF solution. Aqueous dispersions of the doped particles exhibit characteristic red emission under UV light irradiation. The luminescence intensity increases linearly with Eu(tta)(3)phen content, indicating the absence of self-quenching despite the relatively high local concentrations within the particles.     

Fast transfer process of pyrene between oil-in-water miniemulsion droplets

Recently phase formation mechanisms have been estimated by using various fluorescent probes. In this report, the mixing process between internal phases of oil-in-water miniemulsions is discussed for two-dimensional color graphics data (two-dimensional fluorescence images) based on the excimer formation of pyrene as a hydrophobic fluorescent probe. Just after miniemulsion solution B (water, oil, and nonionic surfactant) was gradually added to miniemulsion A (water, oil, surfactant, and trace amount of pyrene) with gentle and careful stirring, the fluorescence spectra and the two-dimensional image of pyrene were measured. The decreasing of the excimer peak of pyrene was observed as soon as miniemulsion solution B was added. The result showed that pyrene initially located in miniemulsion droplets was smoothly diluted by the addition of miniemulsion droplets which contain only oil in the internal phase. The internal phases of miniemulsion droplets are miscible without changing the droplet diameter, and it is declared that pyrene transfers smoothly to the interface between droplets stabilized by the nonionic surfactant because the droplet diameter showed no significant difference throughout this mixing process. Received: 7 December 1999 Accepted: 11 April 2000