Polymer nanoparticles: Preparation techniques and size-control parameters

Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1) and a human alveolar epithelial type II cell line (A549). In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis) and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis). Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

/pdf/different-endocytotic-uptake-mechanisms-for-nanoparticles-in-3mkk80eiwf.pdf

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

The miniemulsion technique is a particular case in the family of heterophase polymerizations, which allows the formation of functionalized polymers by polymerization or modification of polymers in stable nanodroplets. We present here an overview of the different polymer syntheses within the miniemulsion droplets as reported in the literature, and of the current trends in the field.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-6-130.pdf

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers.

Poly(methyl methacrylate) (PMMA) is one of the most widely explored biomedical materials because of its biocompatibility, and recent publications have shown an increasing interest in its applications as a drug carrier. PMMA-based particulate carriers (PMMA(P)) can be prepared either by polymerization methods or from pre-formed polymer-based techniques. Potential biomedical application of these particles includes their use as adjuvant for vaccines and carrier of many drugs as antibiotics and antioxidants via different routes of administration. Release of drugs from PMMA(P) occurs typically in a biphasic way with an incomplete drug release. To improve release profiles, recent strategies are focusing on increasing polymer hydrophilicity by synthesizing functionalized PMMA microspheres or by formulating PMMA composites with hydrophilic polymers. This review examines the current status of preparation techniques, drug release kinetics, biomedical applications and toxicity of these nano/micro PMMA-based particulate carriers.

Poly(methyl methacrylate) particulate carriers in drug delivery

The miniemulsions process represents a versatile tool for the formation of polymeric nanoparticles consisting of different kinds of polymer as obtained by a variety of polymerization types ranging from radical, anionic, cationic, enzymatic polymerization to polyaddition, and polycondensation. The process perfectly allows the encapsulation of hydrophilic and hydrophobic liquids and solids in polymeric shells, molecularly dissolved dyes or other components. In combination with a specific functionalization of the nanoparticles' or nanocapsules' surfaces and the possibility to release substances in a defined way from the interior, complex nanoparticles or nanocapsules are obtained, which are ideally suited for application in biomedical application as marker and targeted drug-delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 493–515, 2010

From Polymeric Particles to Multifunctional Nanocapsules for Biomedical Applications Using the Miniemulsion Process

Phosphonate-functionalized polymer nanoparticles were synthesized by free-radical copolymerization of vinylphosphonic acid (VPA) with styrene or methyl methacrylate (MMA) using the miniemulsion technique. The influence of different parameters such as monomer and surfactant type, amount of vinylphosphonic acid on the average particle size, and size distribution was studied using dynamic light scattering and transmission electron microscopy. Depending on the amount and type of the surfactant used (ionic or non-ionic), phosphonate-functionalized particles in a size range from 102 to 312 nm can be obtained. The density of the phosphonate groups on the particle surface was higher in the case of using MMA as a basis monomer than polystyrene. The kinetic behavior of VPA copolymerization with styrene or MMA using a hydrophobic initiator was investigated by reaction calorimetry. Different kinetic curves were observed for miniemulsion (co)polymerization of styrene- and MMA-based nanoparticles indicating different nucleation mechanisms.

/pdf/synthesis-of-phosphonate-functionalized-polystyrene-and-poly-k5c4ouap3k.pdf

Synthesis of phosphonate-functionalized polystyrene and poly(methyl methacrylate) particles and their kinetic behavior in miniemulsion polymerization

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Synthesis of phosphonate-functionalized polystyrene and poly(methyl methacrylate) particles and their kinetic behavior in miniemulsion polymerization