Polymeric nanoparticles in the diagnosis and treatment of myocardial infarction: Challenges and future prospects

Fig. 1. Schematic representation of the temporal evolution of response to a myocardial infarct. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 2. Schematic representations of the two types of polymeric nanoparticles: nanospheres and nanocapsules. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 3. Schematic representation of the preparation of polymeric nanoparticles by the emulsion polymerization technique. Dispersion of monomers with the surfactant and water solution leads to the formation of large monomer droplets. The excessive amounts of surfactant also form micelles in water. Polymerization starts by diffusion of monomers from the large monomer droplets to the micelles. Afterwards, nucleation occurs by collision of the initiator molecule with the monomers within the micelles and is repeated continuously as more monomers migrate into the micelles to form a polymer particle. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 4. Schematic representation of the preparation of polymeric nanoparticles by the mini-emulsion polymerization technique. The reaction mixture consisting of monomers, surfactant, co-stabilizer, and initiator, is miniemulsified by ultrasonication to form stable monomer droplets. Nucleation occurs by collision of the initiator with the monomers within the droplets and is repeated continuously throughout polymerization. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 5. Schematic representation of the preparation of polymeric nanoparticles by the micro-emulsion polymerization technique. The reaction mixture of vinyl monomers and surfactant is microemulsified to form micelles. Initiators collide with the monomers to start the nucleation and form polymer particles. The nucleated particles continue to grow by diffusion of monomers from other inactive micelles. The polymer particles continue growing until depletion of the micelle reservoir and formation of the final latex. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 6. Schematic representation of the preparation of polymeric nanoparticles by the interfacial polymerization technique. Two reactive monomers dissolved respectively in organic and aqueous solutions are emulsified by sonication to form O/W emulsions. The polymerization reaction takes place at the interface of the two immiscible liquids, promotes wall thickening and allows the formation of nanocapsules. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 7. Schematic representation of the preparation of polymeric nanoparticles by the controlled radical polymerization technique. Initiation begins as cleavage of the initiator generates a reactive free radical which reacts with the monomer. The monomer is hence activated from its dormant state. During the propagation phase additional molecules of monomer are added in a sequential manner to produce a growing polymer chain. Termination occurs when two free radicals react to form a stable non-radical adduct. The end-product is then subject to a combination or disproportionation reaction. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 8. Schematic representation of the preparation of w/o/w double emulsion nanoparticles by the solvent evaporation technique. An aqueous phase (W1) consisting of the drug, polymer, and lipophilic surfactant is emulsified by ultrasonicaton with an oil phase (O) containing a polymer dissolved in an organic solvent. A second aqueous phase (W2) containing a hydrophilic surfactant is then added dropwise to the primary emulsion and further emulsified by ultrasonication. The obtained double emulsion is left on a stirrer to allow solvent evaporation and solidification of the polymeric NPs. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 9. Schematic representation of the preparation of o/w emulsion nanoparticles by the salting-out technique. An oil phase (O) containing the drug and polymer of choice is emulsified with an aqueous phase (W) consisting of a surfactant and salting-out agent added at high concentration. An excessive volume of distilled water is added to the O/W emulsion to precipitate the NPs. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 10. Schematic representation of the preparation of o/w emulsion nanoparticles by the nanoprecipitation technique. An oil phase (O) consisting of the drug and polymer dissolvent in a semipolar organic solvent is slowly added via a syringe pump to an aqueous solution (W) containing a surfactant. NPs are formed upon precipitation of the polymer and diffusion of the organic solvent. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 11. Schematic representation of the preparation of polymeric nanoparticles by the dialysis technique. A lipophilic polymer is dissolved along with the drug of choice in a water miscible organic solvent. The solution is then transferred to a semi-permeable dialysis tubing which is placed in an aqueous solution non-miscible with the polymer. Upon diffusion of the organic solvent to the aqueous phase by osmosis, the polymer aggregates and allows the formation of NPs. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

Fig. 12. Schematic representation of the preparation of polymeric nanoparticles by the supercritical fluid technique: RESS (a) and RESOLV (b). (a) An SCF such as CO2 is pumped to a high-pressure mixing cell containing the polymer of choice. SCF-CO2 dissolves the polymer, and the solution is pushed to a pre-expansion unit where it is heated isobarically to the supercritical temperature. The solution is then depressurized through a nozzle from which it can expand into an expansion vessel and promote formation of NPs by nucleation. (b) An SCF such as CO2 is pumped to a high-pressure mixing cell containing the polymer of choice. SCF-CO2 dissolves the polymer, and the solution is pushed to a pre-expansion unit where it is heated isobarically to the supercritical temperature. SCF is expanded into a liquid solvent immiscible with the polymer which promotes precipitation of the NPs. Parts of the figure were drawn by using pictures from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).