Publications
93 results found
Constantinou AP, Somuncuoğlu B, Georgiou TK, 2024, An environmentally friendly synergistic stabilization of emulsions using an <scp>ABC</scp> macrosurfactant and hydroxypropyl methylcellulose, Journal of Polymer Science, ISSN: 2642-4150
<jats:title>Abstract</jats:title><jats:p>Here, a series of non‐ionic ABC based on the hydrophilic oligo‐ and di‐(ethylene glycol) methyl ether methacrylate (OEGMA300/A and DEGMA/C), and the hydrophobic <jats:italic>n</jats:italic>‐butyl methacrylate (BuMA, B) are investigated as macrosurfactants. Polymers of constant composition, and four varying molar masses (MM) were synthesized via group transfer polymerization. The higher the MM, the bigger the micelles in aqueous media, and the lower the critical micellization concentration and the stability of oil‐in‐water emulsions. The best‐performing macrosurfactant was investigated under different conditions and it was proven that the oil phase volume fraction, and surfactant concentration strongly control the emulsion stability. The macrosurfactants show minimal dependence on the salinity of the water phase, thus offering suitability in preparation of emulsion in environments with different hardness. Emulsions stabilized by both the macrosurfactant and hydroxypropyl methylcellulose (HPMC), a naturally derived viscosity modifier, present a classical non‐Newtonian behavior; the viscosity increased when increasing the MM of the HPMC. The emulsion stabilization is attributed to the synergistic steric stabilization provided by the macrosurfactant and the increased viscosity and formation of an entangled network by HPMC. This formulation leads to emulsion stability over 65% 1 year after emulsification, highlighting its potential use in commercial applications.</jats:p>
Wang L, Constantinou AP, Li Y, et al., 2024, A library of thermoresponsive diblock and statistical copolymers: Unravelling the effect of molar mass, European Polymer Journal, Vol: 207, ISSN: 0014-3057
In the past decades, thermoresponsive polymers have emerged as smart sensing units and promising candidates for a variety of biomedical applications, including targeted drug delivery and tissue engineering. Designing a well-defined thermoresponsive polymer that is versatile for applications requires a systematic study of its properties against its polymeric parameters (i.e., molar mass, composition, and architecture). In terms of the effect of molar mass (MM), previous studies mainly focused on thermoresponsive homopolymers, while the thermoresponsive behaviour of diblock copolymers remained less explored. In this study, we have successfully synthesised 14 different copolymers based on the ionic and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and methyl methacrylate (MMA) and 14 different copolymers based on the non-ionic and thermoresponsive oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol−1 (OEGMA300) and MMA, in both diblock and statistical forms. Their molar masses were varied from 3000 g mol−1 up to 43 000 g mol−1, and their thermoresponsive and self-assembly behaviours in aqueous solutions were carefully characterised. Intriguingly, DMAEMA-based copolymers demonstrated an increase in cloud point temperature (Tcp) with MM in diblock structures, but a decrease in statistical structures. Conversely, OEGMA300-based copolymers initially exhibit an increase in Tcp as the MM increases, particularly at lower MMs, and then reach a plateau with only slight changes at higher MMs, irrespective of their architecture. This investigation not only explores the impact of MM on these thermoresponsive polymers but also contributes to the future design and application of these comonomers, owing to their wide versatility and established research interest in the biomedical field.
Li Q, Wang R, Lee J, et al., 2023, Thermogels based on biocompatible OEGMA-MEGMA diblock copolymers, European Polymer Journal, Vol: 194, Pages: 1-11, ISSN: 0014-3057
A series of biocompatible thermoresponsive copolymers were successfully synthesised via group transfer polymerisation (GTP) from methoxy ethylene glycol methacrylate (MEGMA) and methoxy oligo (ethylene glycol) methacrylate (OEGMA, Mn=300 g mol -1). Statistical and diblock copolymers with molar mass around 8100 g mol-1 and various compositions were investigated. Specifically, the content in OEGMA and MEGMA was varied from 80-20, 70-30, 60-40, to 50-50 w/w%. The thermoresponsive and self-assembly behaviour of the copolymers was investigated through visual tests, rheology, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Interestingly, the diblock copolymers with higher MEGMA content were able to form gels at relatively low concentrations (as low as 5% w/w) when increasing the temperature, something that is reported for the first time for linear ethylene glycol based copolymers. A transition of spherical micelle to worm-like micelle was observed in these diblock copolymers that promotes gelation. Furthermore, these in-house synthesised polymers were mixed with Pluronic® F127. It was found that the gelation area of Pluronic® F127 was broadened by the addition of the synthesised copolymers with one formulation, specifically a combination of 12.5% w/w Pluronic® F127 and 12.5% w/w of a statistical OEGMA-co-MEGMA, forming a stable gel from 34°C to 48°C that is a desirable temperature range for biological applications. Finally, cell viability experiments were performed for the three most promising diblock copolymers was investigated and they were confirmed to be non-toxic.
Shmool TA, Martin LK, Jirkas A, et al., 2023, Unveiling the Rational Development of Stimuli-Responsive Silk Fibroin-Based Ionogel Formulations, CHEMISTRY OF MATERIALS, Vol: 35, Pages: 5798-5808, ISSN: 0897-4756
Correia JS, Miron Barroso S, Hutchings C, et al., 2023, How does the polymer architecture and position of cationic charges affect cell viability?, Polymer Chemistry, Vol: 14, Pages: 303-317, ISSN: 1759-9954
Polymer chemistry, composition and molar mass are factors that are known to affect cytotoxicity however the influence of polymer architecture has not been investigated systematically. In this study the influence of the position of the cationic charges along the polymer chain on cytotoxicity was investigated while keeping constant the other polymer characteristics. Specifically, copolymers of various architectures, based on a cationic pH responsive monomer, 2-(dimethylamino)ethyl methacrylate (DMAEMA) and a non-ionic hydrophilic monomer, oligo(ethylene glycol)methyl ether methacrylate (OEGMA) were engineered and their toxicity towards a panel of cell lines investigated. Of the seven different polymer architectures examined, the block-like structures were less cytotoxic than statistical or gradient/tapered architectures. These findings will assist in developing future vectors for nucleic acid delivery.
Constantinou AP, Wang L, Wang S, et al., 2022, Thermoresponsive block copolymers of increasing architecture complexity: a review on structure-property relationships, Polymer Chemistry, Vol: 14, Pages: 223-247, ISSN: 1759-9954
Thermogels are an exciting class of stimuli responsive materials with many promising applications ranging from the medical field to additive manufacturing. This review focuses on the structure–property relationship of thermoresponsive block copolymers, with emphasis on the effect of architecture. Polymers based on Pluronic®, N-isopropylacrylamide, oligo(ethylene glycol) (meth)acrylate units, and 2-oxazoline units, which are amongst the most studied thermoresponsive units, are discussed. The effect of the polymer's architecture is crucial for controlling the thermoresponsive properties, such as cloud point and gelation temperature.
Mirón-Barroso S, Correia JS, Frampton AE, et al., 2022, Polymeric carriers for delivery of RNA cancer therapeutics, Non-Coding RNA, Vol: 8, Pages: 58-58, ISSN: 2311-553X
As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has ‘druggable’ active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.
Sgro A, Blanco-Colino R, Ahmed WUR, et al., 2022, Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study, BRITISH JOURNAL OF SURGERY, Vol: 109, Pages: 520-529, ISSN: 0007-1323
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Shmool TA, Constantinou A, Jirkas A, et al., 2022, Next generation strategy for tuning the thermoresponsive properties of micellar and hydrogel drug delivery vehicles using ionic liquids, Polymer Chemistry, Vol: 13, Pages: 2340-2350, ISSN: 1759-9954
Amongst the greatest challenges in developing injectable controlled thermoresponsive micellar and hydrogel drug delivery vehicles include tuning the cloud point (CP) and reducing the gelation temperature (Tgel), below 37 °C, without compromising stability and solubility. Here, a unique strategy is employed using ionic liquid (IL) matrices to produce stable micellar and hydrogel delivery vehicles of distinct thermoresponsive properties. Each formulation includes the in-house synthesised polymer OEGMA30020-b-BuMA22-b-DEGMA11 with FITC-IgG. Both micellar-IL and hydrogel-IL formulations exhibit enhanced stability following 120 days of storage under 4 °C compared to in phosphate buffered saline (PBS). Visual tests demonstrate that the CP of the micellar-IL carriers can be finely tuned (31- 46 °C). Rheology measurements show that hydrogel strength is significantly increased and Tgel is reduced, from 40 °C in PBS to 30 °C with IL. Finally, a unique stabilisation mechanism is proposed, triggered by the synergetic action of the excipients and IL in each system
Li Q, Wang L, Chen F, et al., 2022, Thermoresponsive oligo(ethylene glycol) methyl ether methacrylate based copolymers: composition and comonomer effect, Polymer Chemistry, Vol: 13, Pages: 2506-2518, ISSN: 1759-9954
Thermoresponsive polymers based on oligo(ethylene glycol) (OEG) methyl ether methacrylate monomers have drawn much attention in recent years. In this investigation, copolymers based on oligo(ethylene glycol) methyl ether methacrylate (OEGMA, 300 g mol-1) and di(ethylene glycol) methyl ether methacrylate (DEGMA) or/and n-butyl methacrylate (n-BuMA) were successfully synthesised via group transfer polymerisation (GTP). The molar mass was kept constant around 10000 g mol-1, while the OEGMA content was varied from 80% w/w to 50% w/w. Three different structures including diblock bipolymer, diblock terpolymer and statistical copolymers were synthesised and compared. The thermoresponsive properties of the copolymers were investigated in deionised water and phosphate buffered saline (PBS), and in aqueous mixtures with Pluronic® F127. Interestingly, while the diblock polymers based on OEGMA and DEGMA were not able to form gel upon heating, they were found to lower the critical gelation concentration (CGC) of Pluronic® F127 from 15% w/w to 10% w/w and increase the gelation temperature from room temperature to near body temperature.
Constantinou AP, Nele V, Doutch JJ, et al., 2022, Investigation of the thermogelation of a promising biocompatible ABC triblock terpolymer and its comparison with pluronic F127, Macromolecules, Vol: 55, Pages: 1783-1799, ISSN: 0024-9297
Thermoresponsive polymers with the appropriate structure form physical networks upon changes in temperature, and they find utility in formulation science, tissue engineering, and drug delivery. Here, we report a cost-effective biocompatible alternative, namely OEGMA30015-b-BuMA26-b-DEGMA13, which forms gels at low concentrations (as low as 2% w/w); OEGMA300, BuMA, and DEGMA stand for oligo(ethylene glycol) methyl ether methacrylate (MM = 300 g mol–1), n-butyl methacrylate, and di(ethylene glycol) methyl ether methacrylate, respectively. This polymer is investigated in depth and is compared to its commercially available counterpart, Poloxamer P407 (Pluronic F127). To elucidate the differences in their macroscale gelling behavior, we investigate their nanoscale self-assembly by means of small-angle neutron scattering and simultaneously recording their rheological properties. Two different gelation mechanisms are revealed. The triblock copolymer inherently forms elongated micelles, whose length increases by temperature to form worm-like micelles, thus promoting gelation. In contrast, Pluronic F127’s micellization is temperature-driven, and its gelation is attributed to the close packing of the micelles. The gel structure is analyzed through cryogenic scanning and transmission electron microscopy. Ex vivo gelation study upon intracameral injections demonstrates excellent potential for its application to improve drug residence in the eye.
Constantinou AP, Tall A, Li Q, et al., 2022, Liquid–liquid phase separation in aqueous solutions of poly(ethylene glycol) methacrylate homopolymers, Journal of Polymer Science, Vol: 60, Pages: 188-198, ISSN: 2642-4150
Here, the liquid–liquid phase separation (LLPS) in aqueous solutions containing poly(ethylene glycol) (PEG) methacrylate homopolymers is reported for the first time. In this study, the thermoresponse of concentrated solutions of DEGMA60 (two ethylene glycol, EG, groups) TEGMA71 (three EG groups), OEGMA300x (4.5 in average EG groups) of varying molar masses (MM), and OEGMA50028 (nine in average EG groups) is discussed. Interestingly, the temperature of LLPS (TLLPS) is controlled by the length of the PEG side chain, the MM of the OEGMA300x and the polymer concentration. More specifically, the transition temperature decreases with: (i) Decrease in the length of the PEG side chain, (ii) increase in MM of the OEGMA300x, and increase in concentration. In addition, LLPS is also observed in mixtures of OEGMA300x with Pluronic® F127. In conclusion, these systems present a thermally induced LLPS, with the transition temperature being finely tuned to room temperature when DEGMA is used. These systems find potential use in numerous applications, varying from purification to “water-in-water” emulsions.
Lee Y, Lester D, Jones J, et al., 2021, Effect of polymer molecular mass and structure on the mechanical properties of polymer-glass hybrids, ACS Omega, Vol: 7, Pages: 786-792, ISSN: 2470-1343
Organic–inorganic hybrid materials are a promising class of materials for tissue engineering and other biomedical applications. In this systematic study, the effect of the polymer molecular mass (MM) with a linear architecture on hybrid mechanical properties is reported. Well-defined linear poly(methyl methacrylate-co-(3-(trimethoxysilyl)propyl methacrylate)) polymers with a range of MMs of 9 to 90 kDa and one 90 kDa star-shaped polymer were synthesized and then used to form glass–polymer hybrids. It was demonstrated that increasing linear polymer MM decreases the resultant hybrid mechanical strength. Furthermore, a star-polymer hybrid was synthesized as a comparison and demonstrated significantly different mechanical properties relative to its linear-polymer counterpart.
Constantinou AP, Georgiou TK, 2021, Pre‐clinical and clinical applications of thermoreversible hydrogels in biomedical engineering: a review, Polymer International, Vol: 70, Pages: 1433-1448, ISSN: 0959-8103
Thermoreversible polymer hydrogels (TRGs) are physical aqueous networks triggered by temperature, that find potential applications in tissue engineering (TE) and drug/gene delivery. When systems with lower critical solution temperature (LCST) behaviour are used, the aqueous solution of polymer is mixed with cells or drugs/genes, depending on the desired application, at room temperature and then injected in vivo to form a hydrogel. This in-situ forming hydrogel acts as a matrix for tissue regeneration or controlled and targeted release of the compound. This review focuses on discussing the studies in which synthetic TRGs with LCST behaviour have been applied in vivo in model animals. These studies are categorised depending on the general structure of the polymer, as follows: i) poloxamer (also known as Pluronics®), ii) degradable polymers, iii) poly(N-isopropylacrylamide) (PNIPAAm), iv) poly(organophosphazene), and v) poly(2-ethyl-2-oxazoline). In general, when the system is optimised, TRGs provide sustained and topical release of the drugs, thus minimising the undesired side effects. When applied in the TE field, tissue formation was observed. Interestingly, two polymers have reached clinical trials, namely poloxamer 407 (P407, Pluronic® F127, often combined with P188, F68), and Regel® (the formulation of Regel® with the anticancer agent paclitaxel is known as Oncogel®), indicating the challenges need to be overcome before successful application in clinics.
Constantinou AP, Provatakis N, Li Q, et al., 2021, Homopolymer and ABC triblock copolymer mixtures for thermoresponsive gel formulations, Gels, Vol: 7, Pages: 1-11, ISSN: 2310-2861
Our group has recently invented a novel series of thermoresponsive ABC triblock terpolymers based on oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol−1 (OEGMA300, A unit), n-butyl methacrylate (BuMA, B unit) and di(ethylene glycol) methyl ether methacrylate (DEGMA, C unit) with excellent thermogelling properties. In this study, we investigate how the addition of OEGMA300x homopolymers of varying molar mass (MM) affects the gelation characteristics of the best performing ABC triblock terpolymer. Interestingly, the gelation is not disrupted by the addition of the homopolymers, with the gelation temperature (Tgel) remaining stable at around 30 °C, depending on the MM and content in OEGMA300x homopolymer. Moreover, stronger gels are formed when higher MM OEGMA300x homopolymers are added, presumably due to the homopolymer chains acting as bridges between the micelles formed by the triblock terpolymer, thus, favouring gelation. In summary, novel formulations based on mixtures of triblock copolymer and homopolymers are presented, which can provide a cost-effective alternative for use in biomedical applications, compared to the use of the triblock copolymer only.
Zhang X, Contini C, Constantinou A, et al., 2021, How does the hydrophobic content of methacrylate ABA triblock copolymers affect polymersome formation?, Journal of Polymer Science, Vol: 59, Pages: 1724-1731, ISSN: 2642-4169
Polymersomes are exciting self-assembled structures with great potential in pharmaceutical applications. A systematic investigation of a novel series of methacrylate-based polymersomes is reported in this study. Five well-defined ABA triblock copolymers with A being based on tri(ethylene glycol) methyl methacrylate and B being based on 2-(diethylamino)ethyl methacrylate (DMAEMA) were synthesized using a living polymerization method. The effect of the composition of the ABA triblock copolymers on the thickness of the hydrophobic membrane of the polymersomes and the release of a model drug is demonstrated.
Constantinou AP, Zhang K, Somuncuoğlu B, et al., 2021, PEG-based methacrylate tetrablock terpolymers: how does the architecture control the gelation?, Macromolecules, Vol: 54, Pages: 6511-6524, ISSN: 0024-9297
An ABCA tetrablock terpolymer with excellent thermogelling properties in aqueous solutions has been identified by tuning the architecture of ethylene glycol-based tetrablock terpolymers. Specifically, it gels at concentrations as low as 5 wt % at a wide range of temperatures, including body temperature. Nine tetrablock copolymers based on hydrophilic oligo(ethylene glycol) methyl ether methacrylate with average molar mass (MM) 300 g mol–1 (OEGMA300, A), hydrophobic n-butyl methacrylate (BuMA, B), and hydrophilic and thermoresponsive di(ethylene glycol) methyl ether methacrylate (DEGMA, C) were synthesized and screened. The MM and composition were kept constant, while the tetrablock architecture was systematically varied. Specifically, copolymers with (i) two OEGMA300 blocks (ABCA, ABAC, and ACAB), (ii) two BuMA blocks (BACB, BABC, and ABCB), and (iii) two DEGMA blocks (CABC, CACB, and ACBC) were fabricated. The self-assembly and thermoresponsive properties of their aqueous solutions were investigated with the polymer architecture governing their solubility, micellization, thermoresponsive, and rheological properties.
Somuncuoğlu B, Lin Lee Y, Constantinou AP, et al., 2021, Ethyl methacrylate diblock copolymers as polymeric surfactants: effect of molar mass and composition, European Polymer Journal, Vol: 154, Pages: 1-11, ISSN: 0014-3057
Well-defined amphiphilic diblock copolymers and statistical copolymers were synthesised and investigated as polymeric surfactant. Specifically, two series of linear diblock copolymers-totaling 21 copolymer-were studied. In both series, the same hydrophobic monomer (ethyl methacrylate, EtMA) was used, whereas the hydrophilic monomer was changed. The first series was based on the non-ionic hydrophilic monomer, poly(ethylene glycol) methyl ether methacrylate (PEGMA, 300 g/mol), while the second series was based on the ionic, hydrophilic monomer, 2-(dimethylamino)ethyl methyl methacrylate (DMAEMA). The molar mass (MM) and compositions were systematically varied to investigate their effect on the final properties of the polymer. The aqueous solution properties of the copolymers such as their cloud points, effective pKa, hydrodynamic diameters, critical micelle concentrations and hydrophile-lipophile balances were determined. The hydrophobic content affected the thermoresponsive ability and the pKa of the polymer solutions significantly. Finally, the emulsifying properties of block copolymers were studied by preparing emulsions containing 1 w/w% of the polymer at the same water to methyl laurate ratio and observing their stability for 1 month. The stability of the emulsions was affected by both the MM and composition of the polymers but to different extents for the non-ionic compared to the ionic series of polymeric macrosurfactants.
Chung JJ, Yoo J, Sum BST, et al., 2021, 3D printed porous methacrylate/silica hybrid scaffold for bone substitution, Advanced Healthcare Materials, Vol: 10, Pages: 1-13, ISSN: 2192-2640
Inorganic–organic hybrid biomaterials made with star polymer poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) and silica, which show promising mechanical properties, are 3D printed as bone substitutes for the first time, by direct ink writing of the sol. Three different inorganic:organic ratios of poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate)-star-SiO2 hybrid inks are printed with pore channels in the range of 100–200 µm. Mechanical properties of the 3D printed scaffolds fall within the range of trabecular bone, and MC3T3 pre-osteoblast cells are able to adhere to the scaffolds in vitro, regardless of their compositions. Osteogenic and angiogenic properties of the hybrid scaffolds are shown using a rat calvarial defect model. Hybrid scaffolds with 40:60 inorganic:organic composition are able to instigate new vascularized bone formation within its pore channels and polarize macrophages toward M2 phenotype. 3D printing inorganic–organic hybrids with sophisticated polymer structure opens up possibilities to produce novel bone graft materials.
Constantinou A, Patias G, Somuncuoğlu B, et al., 2021, Homo- and co-polymerisation of di(propylene glycol) methyl ether methacrylate – a new monomer, Polymer Chemistry, Vol: 12, Pages: 3522-3532, ISSN: 1759-9954
In this study, a new methacrylate monomer with two propylene glycol groups on the side chain, di(propylene glycol) methyl ether methacrylate (diPGMA), was synthesised via an esterification reaction. This new monomer was homo- and co-polymerised for the first time via group transfer polymerisation (GTP). Nine ABA triblock copolymers were synthesised via a “one-pot” GTP, with A and B blocks being based on the hydrophilic and the thermoresponsive oligo(ethylene glycol) methyl ether methacrylate, average Mn 300 g mol−1 (OEGMA300), and the hydrophobic diPGMA, respectively. The molar mass (MM) and OEGMA300/diPGMA content was systematically varied and the effect of this on the self-assembly and thermoresponsive properties was investigated. All copolymers were shown to self-assemble into aggregates and the size of these aggregates increased with both the MM of the polymer and the polymer content in diPGMA. A thermoresponse was observed in aqueous media, with the cloud point (CP) decreasing as the hydrophobic content increases, and the MM decreases. In concentrated aqueous solutions, the polymer with the highest MM and highest diPGMA content formed gels, whose storage modulus increases as a function of the concentration. This study reports a promising alternative hydrophobic monomer to be used in the fabrication of thermogelling materials.
Constantinou AP, Zhan B, Georgiou TK, 2021, Tuning the gelation of thermoresponsive gels based on triblock terpolymers, Macromolecules, Vol: 54, Pages: 1943-1960, ISSN: 0024-9297
In need of new thermoresponsive gels, a novel combination of repeated units is reported in this study, with the best-performing polymer outperforming the commercial counterpart pluronic F127 by gelling at body temperatures at concentrations as low as 3 w/w%. These polymers are ABC triblock terpolymers of constant molar mass (MM), where A, B, and C blocks consist of hydrophilic oligo(ethylene glycol) methyl ether methacrylate with an average molar mass of 300 g mol–1 (OEGMA300), hydrophobic n-butyl methacrylate (BuMA), and the thermoresponsive di(ethylene glycol) methyl ether methacrylate (DEGMA), respectively. In total, 15 triblock terpolymers were synthesized via group transfer polymerization (GTP), and their composition was systematically varied. Key focus was the characterization of their gelation properties via visual tests and rheological measurements. It was concluded that achieving the optimum hydrophilicity/hydrophobicity ratio is critical to ensure a clear solution to gel transition and a wide gelation area that includes the body temperature.
Li Q, Constantinou A, Georgiou T, 2021, A library of thermoresponsive PEG-based methacrylate homopolymers: How do the molar mass and number of ethylene glycol groups affect the cloud point?, Journal of Applied Polymer Science, Vol: 59, Pages: 230-239, ISSN: 0021-8995
In this study, a novel library of thermoresponsive homopolymers based on poly (ethylene glycol) (EG) (m)ethyl ether methacrylate monomers is presented. Twenty‐seven EG based homopolymers were synthesized and three parameters, the molar mass (MM), the number of the ethylene glycol groups in the monomer, and the chemistry of the functional side group were varied to investigate how these affect their thermoresponsive behavior. The targeted MMs of these polymers are varied from 2560, 5000, 8200 to 12,000 g mol−1. Seven PEG‐based monomers were investigated: ethylene glycol methyl ether methacrylate (MEGMA), ethylene glycol ethyl ether methacrylate (EEGMA), di(ethylene glycol) methyl ether methacrylate (DEGMA), tri(ethylene glycol) methyl ether methacrylate (TEGMA), tri(ethylene glycol) ethyl ether methacrylate (TEGEMA), penta(ethylene glycol) methyl ether methacrylate (PEGMA), nona(ethylene glycol) methyl ether methacrylate (NEGMA). Homopolymers of 2‐(dimethylamino) ethyl methacrylate (DMAEMA) were also synthesized for comparison. The cloud points of these homopolymers were tested in different solvents and it was observed that it decreases as the number of EG group was decreased or the MM increased. Interestingly, the end functional group (methoxy or ethoxy) of the side group has an effect as well and is even more dominant than the number of EG groups.
Alzahabi KH, Usmani O, Georgiou TK, et al., 2020, Approaches to treating tuberculosis by encapsulating metal ions and anti-mycobacterial drugs utilizing nano- and microparticle technologies, Emerging Topics in Life Sciences, Vol: 4, Pages: 581-600, ISSN: 2397-8554
Tuberculosis (TB) is caused by a bacterial infection that affects a number of human organs, primarily the lungs, but also the liver, spleen, and spine, causing key symptoms of fever, fatigue, and persistent cough, and if not treated properly, can be fatal. Every year, 10 million individuals become ill with active TB resulting with a mortality approximating 1.5 million. Current treatment guidelines recommend oral administration of a combination of first-line anti-TB drugs for at least 6 months. While efficacious under optimum conditions, ‘Directly Observed Therapy Short-course’ (DOTS) is not without problems. The long treatment time and poor pharmacokinetics, alongside drug side effects lead to poor patient compliance and has accelerated the emergence of multi-drug resistant (MDR) organisms. All this, combined with the limited number of newly discovered TB drugs to treat MDR-TB and shorten standard therapy time, has highlighted the need for new targeted drug delivery systems. In this respect, there has been recent focus on micro- and nano-particle technologies to prepare organic or/and metal particles loaded with TB drugs to enhance their efficacy by targeted delivery via the inhaled route. In this review, we provide a brief overview of the current epidemiology of TB, and risk factors for progression of latent stage tuberculosis (LTBI) to the active TB. We identify current TB treatment regimens, newly discovered TB drugs, and identify studies that have used micro- or nano-particles technologies to design a reliable inhalation drug delivery system to treat TB more effectively.
Li Volsi A, Tallia F, Iqbal H, et al., 2020, Enzyme degradable star polymethacrylate/silica hybrid inks for 3D printing of tissue scaffolds, Materials Advances, Vol: 1, ISSN: 2633-5409
There is unmet clinical need for scaffolds that can share load with the host tissue while biodegrading under the action of enzymes present at the site of implantation. The aim here was to create the first enzyme cleavable inorganic–organic hybrid “inks” that can be 3D printed as scaffolds for bone regeneration. Inorganic–organic hybrids are co-networks of inorganic and organic components. Although previous hybrids performed well under cyclic loads, there was little control over their degradation. Here we synthesised new hybrids able to degrade in response to endogenous tissue specific metallo proteinases (collagenases) that are involved in natural remodeling of bone. Three well-defined star polymers, of the monomer 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and of methyl methacrylate (MMA), of different architectures were prepared by RAFT polymerisation. The linear arms were connected together at an enzyme degradable core using a collagenase cleavable peptide sequence (GLY-PRO-LEU-GLY-PRO-LYS) modified with dimethacryloyl groups as a crosslinker for RAFT polymerisation. The effect of polymer architecture, i.e. the position of the TMSPMA groups on the polymers, on bonding between networks, mechanical properties, biodegradation rate and 3D printability, via direct ink writing, was investigated for the first time and was proven to be critical for all three properties. Specifically, hybrids made with star polymers with the TMSPMA close to the core exhibited the best mechanical properties, improved printability and a higher degradation rate.
Constantinou AP, Lan T, Carroll DR, et al., 2020, Tricomponent thermoresponsive polymers based on an amine-containing monomer with tuneable hydrophobicity: Effect of composition, European Polymer Journal, Vol: 130, ISSN: 0014-3057
In the present study, six dual-responsive ABC triblock copolymers were synthesised via group transfer polymerisation (GTP) and investigated through visual inspections in terms of their thermoresponsive behaviour. The copolymers consist of i) penta(ethylene glycol) methyl ether methacrylate (PEGMA), which is hydrophilic and thermoresponsive at high temperatures, ii) n-butyl methacrylate (BuMA) as the hydrophobic counterpart to promote self-assembly, and iii) 2-(diethylamino)ethyl methacrylate (DEAEMA), which is pH-responsive by adjusting its hydrophilicity depending on the pH. The effect of the degree of ionisation of DEAEMA units as well as the ionic strength effect on the self-assembly behaviour of the copolymers was tested via dynamic light scattering (DLS). The dissociation constants (pKa) of the amine units of DEAEMA were determined via potentiometric titrations. The thermoresponse has been primarily been investigated in means of cloud points (CPs) at various pH values in deionised water. Detailed phase diagrams were constructed for all the polymer solutions in phosphate buffered saline (PBS), with the interest being focused on the gelation area. It has been clearly proven that gelation is promoted as the content in BuMA and DEAEMA is increased. The polymer that presented the widest gelation area has been further investigated via rheology in terms of its gelation temperature, gelation time and shear-thinning properties.
Constantinou A, Marie-Sainte U, Peng L, et al., 2019, Effect of block copolymer architecture and composition on gold nanoparticle fabrication, Polymer Chemistry, Vol: 10, Pages: 4632-4642, ISSN: 1759-9954
Gold nanoparticles (AuNPs) have many biomedical applications. Their size is a crucial parameter, as it affects cellular uptake. Here, we investigate how the formation of AuNPs is affected by the composition and architecture (AB, BAB and ABA) of the copolymers, which were used as templates for the fabrication of AuNPs.
Mohammed AA, Aviles Milan J, Li S, et al., 2019, Open vessel free radical photopolymerization of double network gels for biomaterial applications using glucose oxidase, Journal of Materials Chemistry B, Vol: 7, Pages: 4030-4039, ISSN: 2050-750X
Polymerization of certain gels in the presence of oxygen can lead to hindered reaction rates and low conversion rates, limiting the use of open vessel polymerization and material synthesis. Here, the oxido-reductase enzyme glucose oxidase (GOx) was used to enable open vessel free radical photopolymerization (FRP) of neutral polyacrylamide (PAAm), and polyelectrolyte poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) under ambient conditions. GOx successfully blocks the inhibition pathways created by O2 in FRP, dramatically increasing the polymer conversion rate for both polymers. In the presence of GOx, PAAm and PAMPS achieved conversion of 78% and 100% respectively at a photoinitiator (PI) concentration of 0.05 wt% with GOx, compared to 0% without GOx at the same PI concentration. Cytotoxicity studies of these polymers show high cell viability after GOx is denatured. Double network hydrogels (DNHGs) were successfully produced using the polymers and use of GOx improved compressive fracture stress by a factor of ten. Vinyl functionalized silica nanoparticles (VSNPs) were used as cross linkers of the first network to further enhance the mechanical properties.
Constantinou A, Sam-Soon N, Carroll D, et al., 2018, Thermoresponsive tetrablock terpolymers: effect of architecture and composition on Gelling behavior, Macromolecules, Vol: 51, Pages: 7019-7031, ISSN: 0024-9297
Thermoresponsive gels are an exciting class of materials with many bioapplications, like tissue engineering and drug delivery, but they are also used in formulation industry and 3-D printing. For these applications to be feasible, the gelation temperature must be tailored. Here, it is reported how the gelation temperature is affected and can be tailored by varying the architecture of tetrablock terpolymers. Specifically, 15 copolymers based on penta(ethylene glycol) methyl ether methacrylate (PEGMA, A block), n-butyl methacrylate (BuMA, B block), and the thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA, C block) were synthesized using group transfer polymerization. Nine tetrablock copolymers of varying architectures, and one triblock copolymer for comparison, with constant molar mass and composition were fabricated. Specifically, the polymers that were investigated are (i) three polymers that contain two A blocks (ABCA, ABAC, and ACAB), (ii) three polymers that contain two B blocks (BACB, BABC, and ABCB), (iii) three polymers that contain two C blocks (CABC, CACB, and ACBC), and (iv) one ABC triblock terpolymer that was synthesized as the control polymer. Then, the five more promising architectures were chosen, and five more polymers with a slightly different composition were synthesized and characterized. Interestingly, it was demonstrated that the block position (architecture) has a significant effect on self-assembly (micelle formation), cloud point, and the rheological and gelling properties of the polymers with two of the tetrablocks showing promise as injectable gels. Specifically, the ACBC terpolymer with 20–30–50 w/w % PEGMA–BuMA–DMAEMA formed gels at at lower concentration but at higher temperatures than the ABC triblock copolymer that was synthesized as a control. On the other hand, the BABC terpolymer with 30–35–45 w/w % PEGMA–BuMA–DMAEMA formed gels at the same concentrations as the ABC triblock
Carroll D, Constantinou A, Stingelin N, et al., 2018, Scalable syntheses of well-defined pentadecablock bipolymer and quintopolymer, Polymer Chemistry, Vol: 9, Pages: 3450-3454, ISSN: 1759-9954
The one-pot syntheses of two pentadeca-(15)-block methacrylate-based amphiphilic copolymers, specifically a bipolymer (AB)7A and a quintopolymer (ABCDE)3, are being reported using a fast and easy to scale up procedure that does not require any intermediate purification steps. Both syntheses were carried out using sequential group transfer polymerisation (GTP) and took under 3.5 h. Amino-containing (DMAEMA, DEAEMA), ether (THFMA, MEGMA) and alkyl (EtMA) methacrylates were used to produce the multiblock copolymers with a final Đ < 1.3.
Ellis T, Chiappi M, García-Trenco A, et al., 2018, Multimetallic microparticles increase the potency of rifampicin against intracellular Mycobacterium tuberculosis, ACS Nano, Vol: 12, Pages: 5228-5240, ISSN: 1936-0851
Mycobacterium tuberculosis ( M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug-tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics. In this work, biodegradable multimetallic microparticles (MMPs), containing Ag NPs and ZnO NPs, were developed for use in pulmonary delivery of antituberculous drugs to the endosomal system of M.tb-infected macrophages. Efficient uptake of MMPs by M.tb-infected THP1 cells was demonstrated using an in vitro macrophage infection model, with direct interaction between MMPs and M.tb visualized with the use of electron FIB-SEM tomography. The release of Ag NPs and ZnO NPs within the macrophage endosomal system increased the potency of the model antibiotic rifampicin by as much as 76%, realized through an increase in membrane disorder of intracellular M.tb. MMPs were effective at independently driving membrane destruction of extracellular bacilli located at the exterior face of THP1 macrophages. This MMP system presents as an effective drug delivery vehicle that could be used for the transport of antituberculous drugs such as rifampicin to infected alveolar macrophages, while increasing drug potency. By increasing M.tb membrane permeability, such a system may prove effectual in improving treatment of drug-susceptible TB in addition to M.tb strains considered drug-resistant.
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