Ultrafine Nanoparticles of Poly(Methyl Methacrylate-co-Methacrylic Acid) Loaded with Aspirin

Nanoparticles of the poly(methyl methacrylate-co-methacrylic acid) or copolymer of P(MMA-co-MAA), were prepared by semicontinuous heterophase polymerization; they show a mean diameter of 12 nm and a 1.75 MMA/MAA molar ratio determined by carbon-13 nuclear magnetic resonance. The content of MAA, greater than that of Eudragit S100, copolymer of P(MMA-co-MAA) accepted by the FDA for the preparation of tablets, ensures its biocompatibility and its metabolism without toxic effects. Loaded with up to 22 wt. % aspirin, that is, acetylsalicylic acid (ASA), these nanoparticles increase slightly their size, according to transmission electron microscopy; however, the presence of ASA on the nanoparticle surface decreases their stability, which leads to a certain aggregation of the particles in the dispersion. Fourier transform infrared spectrometry was used for demonstrating the loading of ASA in the nanoparticles.

Ibuprofen Release from Poly(ethyl cyanoacrylate) Nanoparticles Prepared by Semicontinuous Heterophase Polymerization

Ibuprofen-loaded poly(ethyl cyanoacrylate) nanoparticles were prepared by semicontinuous heterophase polymerization of ethyl cyanoacrylate in the presence of ibuprofen; different surfactant concentration, pH, and temperature were used. Particle size was measured by quasi-light scattering and transmission electron microscopy, while the amount of drug released was determined by UV spectroscopy. Nanoparticles with diameters between 10 and 58 nm, loaded with ibuprofen, were obtained. The smallest particles and the higher drug loading were obtained at the highest pH tested. The analysis of the release data showed that the drug release profiles correspond to the Weibull model. Moreover, it was found that most of the ibuprofen is released within the first 80–120 min; initially the release rate is slow, but then it increases to finally decrease. This behavior contrasts with the reported burst of drug concentration in the plasma after oral administration of IB.

Synthesis, Characterization, and Drug Delivery from pH- and Thermoresponsive Poly(N-Isopropylacrylamide)/Chitosan Core/Shell Nanocomposites Made by Semicontinuous Heterophase Polymerization

Temperature- and pH-responsive core/shell nanoparticles were prepared by semicontinuous heterophase polymerization of N-isopropylacrylamide (NIPA) in the presence of chitosan micelles for drug delivery purposes. Micelles of chitosan, formed in an acetic acid aqueous solution at 70°C containing potassium persulfate, were fed with N-isopropylacrylamide (NIPA) at a controlled rate, to produce PNIPA/chitosan core/shell nanoparticles of about 350 nm. Then, the crosslinking agent, glutaraldehyde, was added to crosslink the nanoparticles. These nanocomposites were temperature- and pH-responsive, which make them suitable as controlled drug releasing agents. The nanoparticles exhibit thermoreversibility to heating-and-cooling cycles and show different responses depending on the releasing medium’s pH. Drug delivery tests were performed, employing as a model drug, doxycycline hyclate.

Biocompatible and Biodegradable Ultrafine Nanoparticles of Poly(Methyl Methacrylate-co-Methacrylic Acid) Prepared via Semicontinuous Heterophase Polymerization: Kinetics and Product Characterization

Ultrafine nanoparticles, less than 10 nm in mean diameter, of the FDA approved copolymer methyl methacrylate- (MMA-)co-methacrylic acid (MAA), 2/1 (mol/mol), were prepared. The method used for the preparation of these particles stabilized in a latex containing around 11% solids includes the dosing of the monomers mixture on a micellar solution preserving monomer starved conditions. It is thought that the operation at these conditions combined with the hydrophilicity of MMA and MAA units favors the formation of ultrafine particles; the propagation reaction carried out within so small compartments renders copolymer chains rich in syndiotactic units very likely as consequence of the restricted movements of the end propagation of the chains. Because of their biocompatibility and biodegradability as well as their extremely small size these nanoparticles could be used as vehicles for improved drug delivery in the treatment of chronic-degenerative diseases.

Preparation and Loading with Rifampicin of Sub-50 nm Poly(ethyl cyanoacrylate) Nanoparticles by Semicontinuous Heterophase Polymerization

We report the preparation of poly(ethyl cyanoacrylate) (PECA) nanoparticles by semicontinuous heterophase polymerization carried out at monomer starved conditions at three monomer addition rates. Particles in the nanometer range were obtained, the size of which diminishes with decreasing monomer addition rate as shown by the fact that particles with mean diameters of ca. 42 and 30 nm were obtained at the faster and intermediate dosing rates, respectively, whereas two populations of particles, one of 15.5 and the other of 36 nm in mean diameters, were produced at the slower dosing rate. The obtained molecular weights were from 2,200 to 3,500 g/mol, depending on the addition rate, which are typical of the anionic polymerizations of cyanoacrylates in aqueous dispersions at low pHs. The rifampicin (RIF) loading into the nanoparticles was successful since the entire drug added was incorporated. The drug release study carried out at pH of 7.2 indicated a faster release from the free RIF at intermediate and larger release times as expected since, in the nanoparticles, first the drug has to diffuse through the nanoparticle structure. The comparison of several drug release models indicates that the RIF release from PECA nanoparticles follows that of Higuchi.

Effect of pH and Monomer Dosing Rate in the Anionic Polymerization of Ethyl Cyanoacrylate in Semicontinuous Operation

Nanoparticles of poly(ethyl cyanoacrylate) with more than 10% solids content were prepared by semicontinuous heterophase polymerization at monomer-starved conditions varying the initial pH in the interval of 1–1.75 and at two monomer dosing rates. Measurements by scanning-transmission electron microscopy allowed us to identify an inverse dependence of particle size on pH. Furthermore, all the polymerizations conducted at the slower monomer dosing rate rendered two particle populations, with the larger one formed from the aggregation of a fraction of the smaller particles. It was believed that the so slow addition of the monomer caused the formation of very small but instable particles, thereby a fraction of which aggregated to reduce the total interface particles-aqueous phase, increasing the latex stability. An increase in the monomer dosing rate led to larger and more stable particles in such way that only one population of nanoparticles with around 40 nm in average diameter was obtained.