RESUMO
Presented in this work is the use of a molecular descriptor, termed the α parameter, to aid in the design of a series of novel, terpene-based, and sustainable polymers that were resistant to biofilm formation by the model bacterial pathogen Pseudomonas aeruginosa. To achieve this, the potential of a range of recently reported, terpene-derived monomers to deliver biofilm resistance when polymerized was both predicted and ranked by the application of the α parameter to key features in their molecular structures. These monomers were derived from commercially available terpenes (i.e., α-pinene, ß-pinene, and carvone), and the prediction of the biofilm resistance properties of the resultant novel (meth)acrylate polymers was confirmed using a combination of high-throughput polymerization screening (in a microarray format) and in vitro testing. Furthermore, monomers, which both exhibited the highest predicted biofilm anti-biofilm behavior and required less than two synthetic stages to be generated, were scaled-up and successfully printed using an inkjet "valve-based" 3D printer. Also, these materials were used to produce polymeric surfactants that were successfully used in microfluidic processing to create microparticles that possessed bio-instructive surfaces. As part of the up-scaling process, a novel rearrangement was observed in a proposed single-step synthesis of α-terpinyl methacrylate via methacryloxylation, which resulted in isolation of an isobornyl-bornyl methacrylate monomer mixture, and the resultant copolymer was also shown to be bacterial attachment-resistant. As there has been great interest in the current literature upon the adoption of these novel terpene-based polymers as green replacements for petrochemical-derived plastics, these observations have significant potential to produce new bio-resistant coatings, packaging materials, fibers, medical devices, etc.
Assuntos
Biofilmes , Terpenos , Terpenos/farmacologia , Polímeros/química , Bactérias , MetacrilatosRESUMO
The versatility of the Passerini three component reaction (Passerini-3CR) is herein exploited for the synthesis of an amphiphilic diblock copolymer, which self-assembles into polymersomes. Carboxy-functionalized poly(ethylene glycol) methyl ether is reacted with AB-type bifunctional monomers and tert-butyl isocyanide in a single process via Passerini-3CR. The resultant diblock copolymer (P1) is obtained in good yield and molar mass dispersity and is well tolerated in model cell lines. The Passerini-3CR versatility and reproducibility are shown by the synthesis of P2, P3, and P4 copolymers. The ability of the Passerini P1 polymersomes to incorporate hydrophilic molecules is verified by loading doxorubicin hydrochloride in P1DOX polymersomes. The flexibility of the synthesis is further demonstrated by simple post-functionalization with a dye, Cyanine-5 (Cy5). The obtained P1-Cy5 polymersomes rapidly internalize in 2D cell monolayers and penetrate deep into 3D spheroids of MDA-MB-231 triple-negative breast cancer cells. P1-Cy5 polymersomes injected systemically in healthy mice are well tolerated and no visible adverse effects are seen under the conditions tested. These data demonstrate that new, biodegradable, biocompatible polymersomes having properties suitable for future use in drug delivery can be easily synthesized by the Passerini-3CR.
Assuntos
Sistemas de Liberação de Medicamentos , Polímeros , Animais , Doxorrubicina/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Reprodutibilidade dos TestesRESUMO
A Passerini three-component polymerization was performed for the synthesis of amphiphilic star-shaped block copolymers with hydrophobic cores and hydrophilic coronae. The degree of polymerization of the hydrophobic core was varied from 5 to 10 repeating units, and the side chain ends were conjugated by performing a Passerini-3CR with PEG-isocyanide and PEG-aldehyde (950 g/mol). The resulting amphiphilic star-shaped block copolymers contained thioether groups, which could be oxidized to sulfones in order to further tune the polarity of the polymer chains. The ability of the amphiphilic copolymers to act as unimolecular micellar encapsulants was tested with the water-insoluble dye Orange II, the water-soluble dye Para Red and the macrolide antibiotic azithromycin. The results showed that the new copolymers were able to retain drug cargo at pH levels corresponding to circulating blood and selectively release therapeutically effective doses of antibiotic as measured by bacterial cell kill. The polymers were also well-tolerated by differentiated THP-1 macrophages in the absence of encapsulated drugs.
Assuntos
Materiais Biocompatíveis/síntese química , Micelas , Nanopartículas/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Azitromicina/administração & dosagem , Azitromicina/química , Linhagem Celular , Liberação Controlada de Fármacos , Humanos , Monócitos/efeitos dos fármacos , Nanopartículas/efeitos adversos , Polietilenoglicóis/química , PolimerizaçãoRESUMO
The precise synthesis of polymers derived from alkyl lactate ester acrylates is reported for the first time. Kinetic experiments were conducted to demonstrate that Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) in alcohols at 25 °C provides a green methodology for the LRP of this forgotten class of biobased monomers. The acrylic derivative of ethyl lactate (EL) solvent and homologous structures with methyl and n-butyl ester were polymerized with excellent control over molecular weight, molecular weight distribution, and chain-end functionality. Kinetics plots in conventional alcohols such as ethanol and methanol were first order in the monomer, with molecular weight increasing linearly with conversion. However, aqueous EL mixtures were found to be more suitable than pure EL to mediate the SET-LRP process. The near-quantitative monomer conversion and high bromine chain-end functionality, demonstrated by matrix-assisted laser desorption ionization time-of-flight analysis, further allowed the preparation of innovative biobased block copolymers containing rubbery poly(ethyl lactate acrylate) poly(ELA) sequences. For instance, the poly(ELA)- b-poly(glycerol acrylate) block copolymer self-assembled in water to form stable micelles with chiral lactic acid-derived block-forming micellar core as confirmed by the pyrene-probe-based fluorescence technique. Dynamic light scattering and transmission electron microscopy measurements revealed the nanosize spherical morphology for these biobased aggregates.
Assuntos
Acrilatos , Lactatos/química , Polímeros/síntese química , Catálise , Cobre/química , Micelas , Polimerização , Polímeros/químicaRESUMO
Metal oxide microparticles with well-defined internal mesostructures are promising materials for a variety of different applications, but practical routes to such materials that allow the constituent structural length scales to be precisely tuned have thus far been difficult to realize. Herein, we describe a novel platform methodology that utilizes self-assembled block copolymer (BCP) microparticles synthesized by dispersion polymerization in supercritical CO2 (scCO2) as universal structure directing agents for both hydrolytic and nonhydrolytic sol-gel routes to metal oxides. Spherically structured poly(methyl methacrylate- block-4-vinylpyridine) (PMMA- b-P4VP) BCP microparticles are translated into a series of the corresponding organic/inorganic composites and pure inorganic derivatives with a high degree of fidelity for the metal oxides TiO2 and LiFePO4. The final products are comprised of particles close to 1 µm in size with a highly ordered internal morphology of interconnected spheres between 20-40 nm in size. Furthermore, our approach is readily scalable, enabling grams of pure or carbon-coated TiO2 and LiFePO4, respectively, to be fabricated in a facile two step route involving ambient temperature mixing and drying stages. Given that both length scales within these BCP microparticles can be controlled independently by minor variations in the reagent quantities used, the present general strategy could represent a milestone in the design and synthesis of hierarchical metal oxides with completely tunable dimensions.
RESUMO
Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived (e.g., vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins.
RESUMO
Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30â¯mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.
Assuntos
Nanopartículas , Poliésteres , Poliésteres/química , Glicerol/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Adipatos , Nanopartículas/químicaRESUMO
Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.
RESUMO
The evaluation of two terpene-derived polymers, termed TPA6 and TPA7, as possible consolidants for archaeological wood was carried out. The overall objective of this work was to expand the non-aqueous treatment toolkit which is available for the conservation of the highly degraded Oseberg collection. The wood artefacts which were found on the Oseberg ship were treated with alum in the early twentieth century, leading to the formation of sulfuric acid and to the precarious state that they are in today. Some of these artefacts cannot be treated with conventional aqueous consolidants, like polyethylene glycol, due to their highly degraded and/or reconstructed nature. This study sought to examine the level of penetration of the polymers in archaeological wood and to evaluate their consolidative effect. Both TPA6 and TPA7 were soluble in isopropanol and had a Mw of 3.9 and 4.2 kDa respectively. A number of archaeological wood specimens were immersed in solutions of these polymers. Their penetration and effects were evaluated using weight and dimensional change, colour change, infrared spectroscopy, scanning electron microscopy and hardness tests. Both polymers successfully penetrated the wood specimens, with a higher concentration found on the surface versus the core. Additionally, both polymers appeared to increase the hardness of the specimen surfaces. Increasing the polymer concentration and soaking time in future investigations could potentially facilitate the penetration to the wood cores.
RESUMO
A new, robust methodology for the synthesis of polystyrene-poly(methyl methacrylate) (PS-PMMA) core-shell particles using seeded dispersion polymerisation in supercritical carbon dioxide is reported, where the core-shell ratio can be controlled predictably via manipulation of reagent stoichiometry. The key development is the application of an iterative addition of the MMA shell monomer to the pre-prepared PS core. Analysis of the materials with differing core-shell ratios indicates that all are isolated as single particle populations with distinct and controllable core-shell morphologies.
RESUMO
Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments.
Assuntos
Glicerol , Nanopartículas , Sistemas de Liberação de Medicamentos , Poliésteres/química , Preparações Farmacêuticas , Adipatos/química , Nanopartículas/química , Portadores de Fármacos/químicaRESUMO
We present a one-pot synthesis for well-defined nanostructured polymeric microparticles formed from block copolymers that could easily be adapted to commercial scale. We have utilized reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare block copolymers in a dispersion polymerization in supercritical carbon dioxide, an efficient process which uses no additional solvents and hence is environmentally acceptable. We demonstrate that a wide range of monomer types, including methacrylates, acrylamides, and styrenics, can be utilized leading to block copolymer materials that are amphiphilic (e.g., poly(methyl methacrylate)-b-poly(N,N-dimethylacrylamide)) and/or mechanically diverse (e.g., poly(methyl methacrylate)-b-poly(N,N-dimethylaminoethylmethacrylate)). Interrogation of the internal structure of the microparticles reveals an array of nanoscale morphologies, including multilayered, curved cylindrical, and spherical domains. Surprisingly, control can also be exerted by changing the chemical nature of the constituent blocks and it is clear that selective CO(2) sorption must strongly influence the block copolymer phase behavior, resulting in kinetically trapped morphologies that are different from those conventionally observed for block copolymer thin films formed in absence of CO(2).
RESUMO
Electrodeposition is a widely used materials-deposition technology with a number of unique features, in particular, the efficient use of starting materials, conformal, and directed coating. The properties of the solvent medium for electrodeposition are critical to the technique's applicability. Supercritical fluids are unique solvents which give a wide range of advantages for chemistry in general, and materials processing in particular. However, a widely applicable approach to electrodeposition from supercritical fluids has not yet been developed. We present here a method that allows electrodeposition of a range of metals from supercritical carbon dioxide, using acetonitrile as a co-solvent and supercritical difluoromethane. This method is based on a careful selection of reagent and supporting electrolyte. There are no obvious barriers preventing this method being applied to deposit a range of materials from many different supercritical fluids. We present the deposition of 3-nm diameter nanowires in mesoporous silica templates using this methodology.
RESUMO
The Oseberg Viking ship burial is one of the most extensive collections of Viking wooden artefacts ever excavated in Norway. In the early twentieth century, many of these artefacts were treated with alum in order to preserve them, inadvertently leading to their current degraded state. It is therefore crucial to develop new bioinspired polymers which could be used to conserve these artefacts and prevent further disintegration. Two hydroxylated polymers were synthesised (TPA6 and TPA7), using α-pinene- and oleic acid-derived monomers functionalised with an acrylate moiety. Characterisation using biomolecular hydrodynamics (analytical ultracentrifugation and high precision viscometry) has shown that these polymers have properties which would potentially make them good wood consolidants. Conformation analyses with the viscosity increment (ν) universal hydrodynamic parameter and ELLIPS1 software showed that both polymers had extended conformations, facilitating in situ networking when applied to wood. SEDFIT-MSTAR analyses of sedimentation equilibrium data indicates a weight average molar mass Mw of (3.9 ± 0.8) kDa and (4.2 ± 0.2) kDa for TPA6 and TPA7 respectively. Analyses with SEDFIT (sedimentation velocity) and MultiSig however revealed that TPA7 had a much greater homogeneity and a lower proportion of aggregation. These studies suggest that both these polymers-particularly TPA7-have characteristics suitable for wood consolidation, such as an optimal molar mass, conformation and a hydroxylated nature, making them interesting leads for further research.
Assuntos
Hidrodinâmica , Polímeros , Ácido Oleico , UltracentrifugaçãoRESUMO
New materials chemistries are urgently needed to overcome the limitations of existing biomedical materials in terms of preparation, functionality and versatility, and also in regards to their compatibility with biological environments. Here, we show that Passerini reactions are especially suited for the preparation of drug delivery materials, as with relatively few steps, polymers can be synthesized with functionality installed enabling drug conjugation and encapsulation, self-assembly into micellar or vesicular architectures, and with facile attachment triggerable chemistries. The polymers can be made with a variety of building blocks and assemble into nanoparticles, which are rapidly internalized in triple negative breast cancer (TNBC) cells. In addition, the polymers transport drug molecules efficiently through 3D cell cultures, and when designed with chemistries allowing pH-mediated release, exhibit greater efficacy against TNBC cells compared to the parent drug.
Assuntos
Nanopartículas , Pró-Fármacos , Neoplasias de Mama Triplo Negativas , Sistemas de Liberação de Medicamentos , Humanos , Polímeros/uso terapêutico , Pró-Fármacos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
N-Hydroxyethyl acrylamide was used as a functional initiator for the enzymatic ring-opening polymerisation of ε-caprolactone and δ-valerolactone. N-Hydroxyethyl acrylamide was found not to undergo self-reaction in the presence of Lipase B from Candida antarctica under the reaction conditions employed. By contrast, this is a major problem for 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate which both show significant transesterification issues leading to unwanted branching and cross-linking. Surprisingly, N-hydroxyethyl acrylamide did not react fully during enzymatic ring-opening polymerisation. Computational docking studies helped us understand that the initiated polymer chains have a higher affinity for the enzyme active site than the initiator alone, leading to polymer propagation proceeding at a faster rate than polymer initiation leading to incomplete initiator consumption. Hydroxyl end group fidelity was confirmed by organocatalytic chain extension with lactide. N-Hydroxyethyl acrylamide initiated polycaprolactones were free-radical copolymerised with PEGMA to produce a small set of amphiphilic copolymers. The amphiphilic polymers were shown to self-assemble into nanoparticles, and to display low cytotoxicity in 2D in vitro experiments. To increase the green credentials of the synthetic strategies, all reactions were carried out in 2-methyl tetrahydrofuran, a solvent derived from renewable resources and an alternative for the more traditionally used fossil-based solvents tetrahydrofuran, dichloromethane, and toluene.
RESUMO
Multifunctional and modular block copolymers prepared from biocompatible monomers and linked by a bioreducible disulfide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block copolymer architecture enabled well-defined nanoparticles to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folate-receptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to nonbioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tunable way.
Assuntos
Técnicas de Transferência de Genes , Nanopartículas/química , Linhagem Celular Tumoral , DNA/química , Ácido Fólico/química , Humanos , Luciferases/análise , Luciferases/metabolismo , Modelos Biológicos , Estrutura Molecular , Plasmídeos/química , Polimerização , Polímeros/síntese química , Polímeros/química , EstereoisomerismoRESUMO
Pseudomonas mendocina was found to produce a unique homopolymer of poly(3-hydroxyoctanoate), P(3HO), rather than a copolymer, when grown on sodium octanoate as the sole carbon source. Although this polymer has been produced by other organisms, interestingly this is the first time an absolute homopolymer has been produced by a wild type organism. In addition, a detailed study on the effects of different extraction methods on the yield, molecular weight, thermal properties, and lipopolysaccharide content of P(3HO) has been carried out. The organism was able to accumulate P(3HO) up to 31.38% of its dry cell weight within 48 h in mineral salt medium. Characterization of the monomer was carried out using FTIR, GC-MS, (13)C, (1)H, and HSQC NMR spectroscopy. The polymer had a crystallinity of 37.5%, Young's modulus value of 11.6 MPa and contact angle of 77.3°. Microstructural studies of solvent cast polymer films revealed a smooth surface topography with a root-mean-square roughness value of 0.238 µm.
Assuntos
Materiais Biocompatíveis/química , Poliésteres/isolamento & purificação , Poli-Hidroxialcanoatos/isolamento & purificação , Pseudomonas mendocina/química , Cristalização , Meios de Cultura/química , Meios de Cultura/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Módulo de Elasticidade , Cromatografia Gasosa-Espectrometria de Massas , Lipopolissacarídeos/análise , Lipopolissacarídeos/biossíntese , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Peso Molecular , Poliésteres/química , Poliésteres/metabolismo , Poli-Hidroxialcanoatos/biossíntese , Poli-Hidroxialcanoatos/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas mendocina/metabolismo , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
PURPOSE: Novel biodegradable and mucoadhesive PLGA/chitosan microparticles with the potential for use as a controlled release gastroretentive system were manufactured using supercritical CO(2) (scCO(2)) by the Particle Gas Saturated System (PGSS) technique (also called CriticalMix(TM)). METHODS: Microparticles were produced from PLGA with the addition of mPEG and chitosan in the absence of organic solvents, surfactants and crosslinkers using the PGSS technique. Microparticle formulations were morphologically characterized by scanning electron microscope; particle size distribution was measured using laser diffraction. Microparticle surface was analyzed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to evaluate the presence of chitosan on the surface. Mucoadhesiveness of the microparticles was evaluated in vitro using a mucin assay employing two different kinds of mucin (Mucin type III and I-S) with different degrees of sialic acid contents, 0.5-1.5% and 9-17%, respectively. RESULTS: The two analytical surface techniques (XPS and ToF-SIMS) demonstrated the presence of the chitosan on the surface of the particles (<100 µm), dependent on the polymer composition of the microparticles. The interaction between the mucin solutions and the PLGA/chitosan microparticles increased significantly with an increasing concentration of mucin and chitosan. CONCLUSIONS: The strong interaction of mucin with the chitosan present on the surface of the particles suggests a potential use of the mucoadhesive carriers for gastroretentive and oral controlled drug release.
Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Adesividade , Animais , Cromatografia com Fluido Supercrítico , Humanos , Microscopia Eletrônica de Varredura , Mucinas/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Propriedades de SuperfícieRESUMO
Injection of polymeric microparticles is the final step in the drug delivery process. Experience has shown that blockage of the syringe mechanism can be a problem under certain conditions leading to poor control of the final product. Particle size and shape are postulated to be significant factors. In this article 2D Discrete element model (DEM) simulations of circles and semi-circles are used to demonstrate the effect of shape on blockage of the syringe mechanism. To corroborate the calculations, a range of experiments on glass spheres and polymers show good agreement with simulations of normally distributed particle sizes. A similar scenario is also briefly modelled in 3D DEM showing similar trends.