Surfactant-free Precipitation Polymerization Research Articles

Synthesis and Formulation of Thermosensitive Drug Carrier for Temperature Triggered Delivery of Naproxen Sodium.

Nanospheres and microspheres are known as a multipurpose compounds and are used in various branches of science. Recent controlled delivery systems for drugs are also based on poly-micro and nanospheres. In our study we describe an investigation of the influence of thermosensitive polymer N-isopropylacrylamide (NIPA) on the release of the drug naproxen sodium (NS) with a hydrogel hydroxypropyl methylcellulose (HPMC) base. The hydrodynamic diameter (DH) of the obtained polymer was measured by using dynamic light scattering (DLS) at a wavelength of 678 nm. Hydrogel formulations of NS were prepared in a specific way ex tempore. NS was sprinkled on the surface of a distilled water, then polymer soluted in water was added. Afterward, HPMC was affixed to the solution. Prepared samples were stored at room temperature for 24 h. Release tests showed that modification of thevcross-linker type influenced the properties of synthesized polymeric particles. The NIPA derivatives obtained via surfactant free precipitation polymerization (SFPP) may be formulated as hydrogel preparations using HPMC. The obtained formulations presented varied half-release times, depending on the type of applied NIPA derivatives in hydrogel formulations. At 18 °C, the release rates were lower comparing to the reference HPMC hydrogel, whereas at 42 °C, the release rates were significantly higher. The synthesized thermosensitive polymers enabled temperature-triggered release of NS.

Functional PMMA nanogels by cross-linking with cyclodextrin methacrylate

Poly(methyl methacrylate) (PMMA) nanogels cross-linked with cyclodextrin-methacrylate (CD-MA) are synthesized by surfactant-free precipitation polymerization. α-, β- and γ-cyclodextrins (CD) are functionalized with methacrylic groups (CD-MAs) with an average amount of vinyl bonds per CD molecule of 2, 4, or 6, and they are used as cross-linker and as complexation unit. The formation and the particle growth correlate with increase of the CD-MA concentration in the reaction mixture. This leads to reduction of the final hydrodynamic radii of the nanoparticles from 363 nm to 36 nm and an improved colloidal stability in the aqueous phase. The number of vinyl groups per CD molecule influences the size of the nanogels, too, and induces the formation of smaller particles with higher cross-linking degree. The PMMA nanogels with CD-MA are swellable in water mixable and water immiscible solvents, their size increases with increase of the portion of organic media. Controlled complexation of guest molecules was achieved by the nanogels in dependence on their CD-MA content and their degree of cross-linking, as shown by studies with phenolphthalein.

Biocompatible and multi-responsive poly(N-vinylcaprolactam)-based microgels: The role of acidic comonomers in the colloidal properties and phase transition as a function of temperature and pH

Stimuli-responsive microgels have great potential for biomedical applications owing to their well-defined structure and tunable swelling-collapse behavior in response to environmental conditions changes. Herein, thermo- and pH-responsive biocompatible microgels have been developed via surfactant-free precipitation polymerization of N-vinylcaprolactam (NVCL) in aqueous media using acrylic or itaconic acid (AA or IA) as acidic comonomers. A comparative study was performed regarding the incorporation of acidic comonomers and their effect on the stimuli-responsive behavior and nanoparticles stability in aqueous dispersion. The particles size, polydispersity as well as temperature- and pH-responsiveness were characterized by Dynamic Light Scattering experiments. The results indicated that the acidic segments in the microgel networks not only rendered pH-responsiveness behavior but were also capable to stabilize the nanoparticles due to the negative charges from carboxyl groups present in AA and IA. Smaller particles diameters were obtained when IA was used as the ionizable comonomer. Moreover, IA proved to be more efficient in the stability of the dispersions against time. The microgels morphology was accessed by Electron Transmission Microscopy, which revealed their spherical shape and low polydispersity, although a tendency for particles aggregation. All microgels were well tolerated by murine peritoneal macrophages, as revealed by cytotoxic tests. These results provide important information for further studies on the incorporation of active ingredients in such microgels for controlled drug release systems.

The Conductivity and pH Values of Dispersions of Nanospheres for Targeted Drug Delivery in the Course of Forced Equilibrium Dialysis.

In the available literature, the problem of pH and conductivity in FED is evaluated separately, and limited mainly to the final purity of the synthesized polymer. In this study data from conductivity and pH measurements were evaluated in the context of the structure of the macromolecule. The aim of the study was to evaluate the conductivity and pH of dispersions of nanospheres synthesized with the use of N-isopropyl acrylamide (NIPA) as the main monomer, N,N'-methylenebisacrylamide (MBA) as the cross-linker and acrylic acid (AcA) as the anionic comonomer during the purification of dispersions via forced equilibrium dialysis (FED). Six batches of nanospheres were obtained in the process of surfactant free precipitation polymerization (SFPP) under inert nitrogen. The conductivity and pH of the dispersions of nanospheres were measured at the beginning of FED and after finishing that process. The conductivity in the systems being studied decreased significantly in the process of FED. The initial values of conductivity ranged from 736.85±8.13 μS×cm(-1) to 1048.90±67.53 μS×cm(-1) After 10 days, when the systems being assessed gained stability in terms of conductivity level, the values of conductivity were between 4.29±0.01 μS×cm(-1) and 33.56±0.04 μS×cm(-1). The pH values inreased significantly after FED. The resulting pH was between 6.92±0.07 and 8.21±0.07, while the initial values were between 3.42±0.23 μS×cm(-1) and 4.30±0.22 μS×cm(-1). Conductivity and pH measurements performed during purification via FED provide important information on the composition of the resulting nanospheres, including the functional groups embedded in the structure of the polymer in the course of the synthesis, as well as the purity of the structures. The presence of a cross-linker and acidic comonomer in the poly-N-isopropyl acrylamide (polyNIPA) macromolecule may be confirmed by both the pH and the conductivity measurements.

Synthesis and characterization of biomimetic nanogels for immunorecognition

Biomimetic nanoparticles are promising materials for biomedical and biotechnological applications. Cationic poly(N-isopropylacrylamide) (PNIPAM) nanogels containing charged amine groups brought by addition of 2-aminoethylmethacrylate hydrochloride (AEMH) or N-(3-aminopropyl) methacrylamide hydrochloride (APMH) as co-monomers were prepared by surfactant-free precipitation polymerization. The influence of the relative amount and mode of addition of the co-monomer on both the size and the amine group density of the nanogel particles was studied. Two nanogels, one prepared using APMH (1%mol/mol NIPAM, in batch) and another with AEMH (2%mol/mol NIPAM, by shot addition) as co-monomers, were selected for the covalent coupling of a Protein L-mimic ligand to free amine groups on the particles. The ability of the synthesized biomimetic nanoparticles for recognizing and binding human IgG (hIgG) molecules was assessed and the selectivity toward immunoglobulin molecules evaluated.

Controlling the Synthesis and Characterization of Micrometer-Sized PNIPAM Microgels with Tailored Morphologies

This Article presents the controlling synthesis and characterization of micrometer-sized, multiresponsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA) microgel particles. By combining semibatch and temperature-programmed surfactant-free precipitation polymerization, we have successfully developed a novel approach to the preparation of temperature- and pH-responsive PNIPAM microgels with a dense-shell (DS), dense-core (DC), or homogeneous (HOMO) structure. We then investigated the interaction between the synthesized microgels and some fluorescent dye molecules using confocal laser scanning microscopy (CLSM). Our results have qualitatively revealed that the cross-linkers and the functional carboxylic groups (-COOH) could be homogeneously distributed, predominately localized inside the core, or concentrated near the surface of the synthesized microgels. Moreover, pH-responsive swelling behaviors of the microgels were investigated and discussed with titration and CLSM data. We found that the swelling capability is strongly dependent on the morphology of the PNIPAM microgel. Besides the absorption of fluorescent molecules, the synthesized microgels also showed a strong affinity for fluorescently labeled polypeptide, even at a relatively high salt concentration.

Aqueous nanogels modified with cyclodextrin

In this work, the incorporation of reactive cyclodextrins (CDs) in aqueous nanogels based on poly( N-vinylcaprolactam) (VCL) is studied by surfactant-free precipitation polymerization process. α-, β-, γ-CDs were functionalized with acrylic groups and the average amount of vinyl bonds per CD molecule was adjusted to 2, 4, or 6. The increase of the CD concentration in the reaction mixture led to the reduction of the final hydrodynamic radius of nanogels from 227 nm to 62 nm. The increase of the vinyl groups number per CD molecule induced formation of smaller nanogels ( R h = 22.5 nm) and considerable increase of the crosslinking degree. Obtained cyclodextrin-modified nanogels show temperature sensitivity in aqueous medium with a volume transition point around 30 °C. The complexation properties of CDs incorporated in nanogel networks were proved by titration with phenolphthalein.

Microgel/clay nanohybrids as responsive scavenger systems

Microgel–clay composite particles were prepared by one-step surfactant–free precipitation polymerization. Laponite nanoparticles present in the reaction mixture become encapsulated during the microgel formation process. Microgel–clay composites based on poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate) containing different amount of incorporated clay nanoparticles were synthesized. The clay content was varied from 2 wt% to 18 wt%. The extremely high incorporation efficiency of the clay nanoparticles into microgels was detected. The size of the hybrid microgels was decreased from 700 nm to 100 nm by increase of the clay concentration in the reaction mixture. Obtained hybrid microgels exhibit negative surface charge and excellent colloidal stability. Microgel–clay composite particles display temperature-sensitive behaviour in water. The swelling degree of the hybrid microgels decreases with increase of the clay loading. Microgel–clay composite particles exhibit temperature-controlled uptake of the cationic dye, Methylene blue, and can be used as scavenger systems in aqueous media.

Synthesis and characterization of hydrogel particles containing Cibacron Blue F3G-A

The analysis of low abundance and low molecular weight biomolecules is challenging due to their labile nature and the presence of high abundance, high molecular weight species such as serum albumin, which can hinder their detection. Functionalized hydrogel particles have proven to be ideally suited for this application. We here report the synthesis of hydrogel core and core–shell particles with incorporated Cibacron Blue F3G-A, and analysis of their harvesting properties. Hydrogel particle scaffolds consisting of cross-linked N-isopropylacrylamide and allylamine copolymers were synthesized via surfactant-free precipitation polymerization, with the blue dye subsequently affixed via a nucleophilic substitution reaction. The dye-functionalized core and core–shell particles were found to efficiently harvest and sequester dilute low molecular weight peptides and proteins from solution, with the core–shell particles more effectively excluding larger proteins. Moreover, proteins bound by core and core–shell particles containing blue dye were protected from tryptic degradation. These findings suggest that core and core–shell hydrogel particles containing Cibacron Blue F3G-A constitute promising new tools for peptide/protein biomarker harvesting applications.

Continuous precipitation polymerization of vinylidene fluoride in supercritical carbon dioxide: molecular weight distribution

The surfactant-free precipitation polymerization of vinylidene fluoride (VF2) in supercritical carbon dioxide was studied in a continuous stirred autoclave. The polymerization temperature ranged from 65 to 85°C, the average residence time in the reactor varied from 10 to 50 min., and the pressure was between 210 and 305 bar. Diethyl peroxydicarbonate was used as the initiator. The fractional conversion of monomer varied from 7 to 26%, the number-average molecular weight of the polymer was between about 14,000 and 79,000, and the weight-average molecular weight was between about 21,000 and 700,000. In many cases, the polymer exhibited a bimodal molecular-weight distribution, especially at high monomer concentrations.

Continuous Precipitation Polymerization of Vinylidene Fluoride in Supercritical Carbon Dioxide: Modeling the Rate of Polymerization

The kinetics of the surfactant-free precipitation polymerization of vinylidene fluoride (VF2) in supercritical carbon dioxide have been studied in a continuous stirred autoclave. Diethyl peroxydicarbonate was used as the free-radical initiator. The stirring rate and agitator design had no effect on the rate of polymerization (Rp) or on the weight-average molecular weight (Mw) of the formed poly(vinylidene fluoride) (PVDF). The fractional conversion of VF2 ranged from 7 to 26%, and Rp was as high as 27 × 10-5 mol/L·s at 75 °C and at a VF2 feed concentration of 2.5 mol/L. The PVDF polymer was collected as a dry, “free-flowing” powder and had Mw's up to 150 kg/mol and melt flow indices as low as 3.0 at 230 °C. Homogeneous, free-radical kinetics provided a reasonable basis for describing the rate of polymerization, despite the heterogeneous nature of the system. The order of the reaction with respect to the monomer was found to be 1.0, and the order with respect to the initiator was 0.5. The experimental data...