Microwave-assisted Ring-opening Polymerization Research Articles

MICROWAVE ASSISTED LACTIDE-GLYCOLIDE HOMO AND COPOLYMERIZATION INITIATED BY MAGNESIUM LACTATE

In this work, microwave-assisted ring opening polymerization (ROP) of lactide (LA) and glycolide (GA) initiated by magnesium lactate was investigated. The influence of microwave power, temperature, and reaction time on homopolymers and copolymer’s structure and thermal properties is discussed. Polymerization of L-lactide (LLA) initiated by the magnesium compound resulted in yields up to 78% and poly(L-lactic acid) (PLLA) with average molar mass of up to 30,600 g mol-1. Homopolymerization of glycolide generate poly(glycolic acid) (PGA) in yields up to 90% and in L-lactide/glycolide copolymerizations yields between 34-82%. PLLA prepared with the initiator presented microstructure with significant amount of stereo errors as the result of a racemization process during polymerization as well as low glass transition temperature (Tg) and melting temperature (Tm), while the PGAs presented high Tg, due to high crystallinity, and Tm in accordance with the literature. LLA and GA copolymerization result in poly(lactic acid-co-glycolic acid) (PLGA) with composition close to polymerization feed composition.

Microwave-assisted synthesis of self-assembling bi-functionalizable amphiphilic diblock copolymers

Active biodegradable polymeric materials are a key area of investigation to develop new imaging and treatment modalities. In this study, we sought to develop tailor-made bi-functionalizable amphiphilic diblock copolymers (BFACs) bearing different reactive groups (e.g., azide, alkyne, maleimide, biotin) on both ends. Designed with a linear backbone constituted of poly (lactic acid), a hydrophobic biodegradable polyester, and poly (ethylene glycol), a hydrophilic biocompatible polymer, BFACs can self-assemble in aqueous media. They are synthesized using a straightforward two-step process: a microwave-assisted ring-opening polymerization followed by a Steglich esterification. BFACs are able to keep their micellar state after the functionalization of their reactive groups via covalent linking or strong interactions with different fluorescent dyes. Interestingly, formation of BFACs-based micelles and their double labeling can be performed in one step. Finally, the uptake of functionalized BFACs-based micelles in the cytoplasmic compartments of MCF-7 cells is observed, thereby illustrating the potential of BFACs to be an easy-to-use tool towards fast development of nanoconstructs for therapy, imaging or theranostics.

Folate-Targeted Cholesterol-Grafted Lipo-Polymeric Nanoparticles for Chemotherapeutic Agent Delivery.

Docetaxel (DTX), an FDA approved chemotherapeutic agent, is used as a first-line treatment for triple-negative breast cancer (TNBC). Its poor aqueous solubility, rapid metabolism, short half-life, and effective targeting to the cancer cells limits its optimal therapeutic use. Herein, we report folate targeted amphiphilic lipopolymer grafted with cholesterol conjugated carbonate and DL-lactide prepared by microwave assisted ring opening polymerization, for the efficient actively targeted delivery of DTX. The DTX-loaded folate-targeted lipopolymeric nanoparticles (F-DTX-LPNs) prepared by the emulsion solvent evaporation method exhibited a smaller size of ∼115.17nm with a PDI of 0.205 and encapsulation efficiency of >80%. Further, these lipopolymeric nanoparticles (F-DTX-LPNs) showed a good on-bench stability and sustained DTX release for 7days. Cell-based assays in MDA-MB-231 cells revealed a significant enhancement in the intracellular uptake of folate-targeted lipopolymeric nanoparticles compared to non-targeted nanoparticles. Further, methyl beta-cyclodextrin (Mβ-CD) completely inhibited the uptake of these nanoparticles in the cells, indicating a lipid raft-mediated uptake mechanism. The developed F-DTX-LPNs showed improved cytotoxicity, apoptosis, and significant fold-change in expression levels of Bcl-2, BAX and Ki-67 as compared to non-targeted DTX-LPNs and free DTX. Further, F-DTX-LPNs showed an improved in vivo pharmacokinetic profile in Sprague Dawley rats as compared to the free DTX. The bio-imaging of ex vivo tissues demonstrated that the DiR loaded folate targeted LPNs exhibited intense signals after 24h because of slow release of DiR dye from the nanoparticles.

Ionic liquid-functionalized LDH as catalytic-initiating nanoparticles for microwave-activated ring opening polymerization of ε-caprolactone

Layered double hydroxides with ionic liquid as highly active catalytic-initiating system for microwave-assisted ring opening polymerization of ε-caprolactone.

Development of resiquimod-loaded modified PLA-based nanoparticles for cancer immunotherapy: A kinetic study

Resiquimod (R848), a member of the imidazoquinoline family, is a Toll-like receptor 7/8 agonist with high potency for cancer immunotherapy. However, tolerance induction and adverse effects limit its development as a drug. Encapsulation in a polymer matrix can circumvent these limitations, as shown in our formerly published approach where R848 was loaded into polylactic acid (PLA)-based nanoparticles (NP). Although the results were encouraging, low rates of encapsulation and rapid release of the drug were observed. In this study, we present a new strategy using mixed NP from modified linear PLA in order to improve the encapsulation and modulate the release profile of R848. Modified PLA polymers were designed and synthesized by microwave-assisted ring opening polymerization of d,l-lactide, using polyethylene glycol as initiator to increase the hydrophilic properties of the polymer or linear saturated aliphatic chains (C8 or C20) to increase the affinity with hydrophobic R848. NP were prepared by solvent evaporation method, leading to particles of 205–288 nm loaded with either R848 or DiO as a tracking agent. The release profile showed longer retention of R848 at both neutral and acidic pH for NP from grafted polymers. Upon exposure to phagocytic immune cells, NP were actively taken up by the cells and no impact on cell viability was observed, independently of the constitutive polymer. All R848-loaded NP activated macrophages to secrete interleukin-6, demonstrating that the drug cargo was immunologically active. Importantly, macrophage activation by NP-delivered R848 was slower than with free R848, in accordance with the in vitro release profiles. Thus, NP prepared from modified PLA polymers showed no signs of toxicity to immune cells and efficiently delivered their immunoactive cargo in a delayed manner. This delivery strategy may enhance the efficacy and safety of small-molecule immunostimulants.

Functional polyhedral oligomeric silsesquioxane reinforced poly(lactic acid) nanocomposites for biomedical applications

Polyhedral oligomeric silsesquioxane reinforced poly (L-lactic acid) nanocomposites (PLLA/POSS) were prepared to overcome the insufficient mechanical properties of PLLA. In order to improve the compatibility between the nanofillers and matrix, PLLA chains were grafted onto the POSS nanoparticles via microwave-assisted ring opening polymerization (ROP). Herein, a series of interface-modified polyhedral oligomeric silsesquioxane (POSS-(PLLA)32) nanoparticles with various PLLA tail lengths were synthesized and the influence of the structure and additional amount of POSS nanoparticles on the properties of PLLA based nanocomposites were studied. POSS nanoparticles exhibit effective nucleation activity and lead to a significant improvement in the mechanical strength, thermal stability and biocompatibility of the resulting nanocomposites. The addition of 6 wt% POSS-(PLLA)32 600 shows the optimal mechanical properties owing to has the longest PLLA tail length on POSS core, which possesses the optimal interfacial compatibility between POSS nanoparticles and PLLA. The Young's modulus improved by 57% and the tensile strength increased by 26.5% compared with neat PLLA. Moreover, the introduction of POSS nanoparticles lead to a porous fiber structure when processed by electrospinning and the nanofibrous scaffold effectively promoted cells adhesion and spreading. These results demonstrate the potential applications of the PLLA/POSS nanocomposites in tissue engineering and regenerative medicine.

Synthesis of Fucoidan-Mimetic Glycopolymers with Well-Defined Sulfation Patterns via Emulsion Ring-Opening Metathesis Polymerization

The approach developed here offers distinct and well-defined glycopolymers for deciphering the biological roles of natural bioactive polysaccharides. Fucose monomers were chemically synthesized and decorated with specific sulfation patterns including unsulfate, monosulfate, disulfate, and trisulfate groups. The six fucoidan-mimetic glycopolymers (18-23) were successfully fabricated through microwave-assisted ring-opening metathesis polymerization (ROMP) in an emulsion system. The molecular weight (Mw), polydispersity index (PDI), and multiple functional groups were fully characterized by SEC-MALLS-RI and NMR spectroscopy. Three glycopolymers (19, 21, 23) associated with 2-O-sulfation exhibited better inhibitory effects on the H1N1 virus, while glycopolymers (19, 20) with monosulfate groups were more effective against the H3N2 virus. These findings would promote the development of novel anti-influenza A virus (IAV) drugs based on natural fucoidans.

Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles

Advantages associated with the use of polylactic acid (PLA) nano- or microparticles as drug delivery systems have been widely proven in the field of pharmaceutical sciences. These biodegradable and biocompatible carriers have demonstrated different loading and release properties depending on interactions with the cargo, preparation methods, particles size or molecular weight of PLA. In this study, we sought to show the possibility of influencing these properties by modifying the structure of the constituting polymer. Seven non-functionalized or functionalized PLA polymers were specifically designed and synthesized by microwave-assisted ring-opening polymerization of d,l-lactide. They presented short hydrophobic and/or hydrophilic groups thanks to the use of C20 aliphatic chain, mPEG1000, sorbitan esters (Spans®) or polysorbates (Tweens®), their PEGylated analogues, as initiators. Then, seven types of drug-loaded nanoparticles (NP) were prepared from these polymers and compared in terms of physico-chemical characteristics, drug loading and release profiles. Although the loading properties were not improved with any of the functionalized PLA NP, different release profiles were observed in an aqueous medium at 37 °C and over a period of five days. The presence of PEG moieties in the core of PLA-polysorbates NP induced a faster release while the addition of a single aliphatic chain induced a slower release due to better interactions with the active molecule.

Development of extended-voyaging anti-oxidant Linked Amphiphilic Polymeric Nanomicelles for Anti-Tuberculosis Drug Delivery

Amphiphilic chitosan-graft-poly(caprolactone)/(ferulic acid) (CS-g-PCL/FA) multi-co-polymers were fabricated by microwave-assisted ring opening polymerization followed by an 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC)-mediated coupling reaction and characterized by Fourier transformed infrared (FTIR) spectroscopy. Graft copolymers self-assembled into nanomicelles, and were able to incorporate rifampicin (RF) into their hydrophobic inner cores. X-ray diffraction (XRD) patterns were applied to characterize the crystal structures of graft polymers and the effects of RF on micelle morphology. Empty and RF-loaded CS-g-PCL/FA nanomicelles underwent swelling and degradation in acidic pH conditions. Scanning electron microscopy, transmission electron microscopy, and dynamic light scattering revealed that the self-assembled, RF-loaded micelles were spherical, with an average size of 100–210nm. An in vitro study conducted at 37°C demonstrated that RF and FA release from micelles at pH 5.3 was much faster than that at pH 7.4. The RF and FA release was significantly accelerated by switching to an acidic pH, owing to swelling of the micelles at lower pH values caused by the rapid degradation of ester and amide bonds present in the micelles. Fluorescence micrographs revealed successful entry of the polymeric micelles into A549cell lines. Thus, graft polymeric micelles have promising potential for delivery of hydrophobic antitubercular drugs and may improve therapeutic approaches for tuberculosis.

Alkylene oxide poylmerizations: identification of side reactions and by-products

In this study microwave-assisted anionic ring opening polymerization (ROP) of alkylene oxides is reported. Low molar mass polymers of propylene oxide (PO), butylene oxide (BO) and hexylene oxide (HO) are synthesized by anionic ring opening using various monohydric alcohols as initiators. The monohydric alcohols and lower molar masses allowed for monitoring of different types of possible unwanted by-products and their sources. Liquid chromatography at critical conditions (LCCC) and liquid adsorption chromatography (LAC) are used to determine the presence of oligomers other than targeted. Finally, MALDI-TOF MS of the products have clearly shown the trends and extents of different types of side reactions that are possible in anionic ring opening of alkylene oxides. Propylene oxide is most vulnerable to chain transfer reactions compared to higher alkylene oxide.

Studies on microwave-assisted ring-opening polymerization and property of poly(9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one)

Poly(9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one) (PPTC) was synthesized by the microwave-assisted ring-opening polymerization (MROP) of a six-membered cyclic carbonate monomer 9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one (PTC) with tin(II) 2-ethylhexanoate (Sn(Oct)2) or aluminum isopropoxide (Al(OiPr)3) as the catalysts. The obtained polycarbonates were further reduced by apalladium/carbonate catalyst (10% Pd/C) to afford partly deprotected polycarbonates containing hydroxyl groups (HPPTC). These two types of polycarbonates were characterized by 1H-NMR, Fourier transform infrared spectroscopy (FTIR), UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and automatic contact-angle measurements. The influence of the feed molar ratio of monomer-to-catalyst, the microwave irradiation power and the reaction time on the polymerization was also studied. The experimental results showed that HPPTC possessed significantly higher hydrophilicity and water absorption rate than PPTC.

Morphometric study of proximal femur in post-menopausal women: A radiological study

Novel imidazoline-functionalized diblock copolymers based on polystyrene (PS) and poly(D,L-lactide) (PLA) were synthesized as precursors to corresponding functional PS-based porous materials through a three-step sequential methodology starting from an asymmetric heterobifunctional initiator. α-Hydroxyl poly(4-cyanostyrene-co-styrene) random copolymers were first obtained via an atom transfer free-radical polymerization (ATRP) procedure by varying the amount of 4-cyanostyrene in the comonomer feed. Cyano groups were then transformed into corresponding imidazoline rings. Subsequently, the microwave-assisted ring-opening polymerization (ROP) of d,l-lactide from the imidazoline-functionalized PS-based macroinitiators allowed for the generation of semi-degradable diblock copolymers with different PLA volume fractions so as to develop microphase-separated morphologies. The precursors and resulting copolymers were analyzed by 1H, 13C NMR, and FT-IR spectroscopy. Upon induced shear-flow via channel-die processing, oriented materials constituted of PLA nanodomains in a polystyrene-based continuous matrix were formed. Hydrolysis in alkaline conditions of the PLA sacrificial block yielded imidazoline-functionalized porous PS-based matrices. The resulting porous frameworks were analyzed by scanning electron microscopy (SEM) and nitrogen sorption porosimetry.

A new route toward imidazoline-functionalized porous polymeric materials from corresponding polystyrene-polylactide diblock copolymers

Novel imidazoline-functionalized diblock copolymers based on polystyrene (PS) and poly(D,L-lactide) (PLA) were synthesized as precursors to corresponding functional PS-based porous materials through a three-step sequential methodology starting from an asymmetric heterobifunctional initiator. α-Hydroxyl poly(4-cyanostyrene-co-styrene) random copolymers were first obtained via an atom transfer free-radical polymerization (ATRP) procedure by varying the amount of 4-cyanostyrene in the comonomer feed. Cyano groups were then transformed into corresponding imidazoline rings. Subsequently, the microwave-assisted ring-opening polymerization (ROP) of d,l-lactide from the imidazoline-functionalized PS-based macroinitiators allowed for the generation of semi-degradable diblock copolymers with different PLA volume fractions so as to develop microphase-separated morphologies. The precursors and resulting copolymers were analyzed by 1H, 13C NMR, and FT-IR spectroscopy. Upon induced shear-flow via channel-die processing, oriented materials constituted of PLA nanodomains in a polystyrene-based continuous matrix were formed. Hydrolysis in alkaline conditions of the PLA sacrificial block yielded imidazoline-functionalized porous PS-based matrices. The resulting porous frameworks were analyzed by scanning electron microscopy (SEM) and nitrogen sorption porosimetry.

Microwave-assisted cationic ring-opening polymerization of 2-oxazolines.

Unlike any other polymer class, the (co-)poly(2-oxazoline)s have tremendously benefited from the introduction of microwave reactors into chemical laboratories. This review focuses on the research activities in the area of (co-)poly(2-oxazoline)s prepared by microwave-assisted syntheses and, correspondingly, summarizes the current-state-of the-art of the microwave-assisted synthesis of 2-oxazoline monomers and the microwave-assisted ring-opening (co-)polymerization of 2-oxazolines as well as prominent examples of post-polymerization modification of (co-)poly(2-oxazoline)s. Special attention is attributed to the kinetic analysis of the microwave-assisted polymerization of 2-oxazolines and the discussion of non-thermal microwave effects.

Green PU resin from an accelerated Non-isocyanate process with microwave radiation

The ring opening between BCC with di-amine by conventional heating (130 °C for 48 h) is a time-consuming and non-efficient process. This work has been aiming at accelerating its ring-opening reaction by a microwave radiation process. Besides, catalyst and solvent selections of this PU reaction system, the microwave power output, radiation time, catalyst and reaction media were major consideration of this research. A catalyst, TBAC or LiBr had been applied on each microwave-assisted ring-opening polymerization of BCC with Jeffamine D-2000. A similar average molecular weight of NH2-PU oligomer was obtained from a 50 min microwave radiation by using 50 W power output. The radiation system with TBAC as catalyst, and it resulted in a formation of NH2-PU oligomer with Mn and Mw were 12,997 and 15,580, and that of 10,882 and 13,508 with LiBr as catalyst. The solvent polarity, catalyst solubility and microwave output energy in this radiation system were considered as important factors for this new green process.

Large-scale microwave-assisted ring-opening polymerization of ɛ-caprolactone

To probe into the industrialization possibility of microwave-assisted ring-opening polymerization (ROP) of ɛ-caprolactone (ɛ-CL), it was performed with monomer mass from 750 to 2450 g using a self-designed industrial microwave oven (6000 W) catalyzed by stannous octanoate (Sn(Oct) 2) ( M/Cat = 1000). The large-scale ROP of ɛ-CL proceeded smoothly at various microwave power levels (850, 1700, and 2550 W) and produced poly(ɛ-caprolactone) (PCL) with weight-average molar mass ( M w) from 66,000 to 12,2000 g/mol within 40 min in a yield over 93%. The structure of PCL was characterized by 1H and 13C NMR, FT-IR, DSC and WAXD. We propose that the microwave ROP of ɛ-CL is a potential technology to prepare PCL commercially.

Rapid synthesis of biodegradable poly(epsilon-caprolactone- co- p-dioxanone) random copolymers under microwave irradiation

Biodegradable poly(epsilon-caprolactone- co- p-dioxanone) (PCDO) random copolymers have been synthesized by ring-opening polymerization of epsilon-caprolactone (CL) and p-dioxanone (PDO) under microwave irradiation. The effects of irradiation time and different CL/PDO molar feed ratios on the microwave-assisted ring-opening polymerization (MROP) of PCDO have been discussed. The resultant products were characterized by 1H NMR, GPC and DSC. It was found that the polymerization was completed within 20 min at 140 °C. In the presence of different CL/PDO molar feed ratios, the conversions of both monomers were kept relatively constant. DSC study suggested that with increasing the content of PDO in the copolymers, the crystalline degree of the copolymers decreased gradually. It is believed to be a promising biodegradable material.

Microwave-assisted ring-opening copolymerization of ɛ-caprolactone and 2-Phenyl-5,5-bis(oxymethyl) trimethylene carbonate

A series of polycarbonate copolymers were synthesized by microwave-assisted ring-opening polymerization of ɛ-caprolactone (CL) and 2-phenyl-5,5-bis(oxymethyl) trimethylene carbonate (PTC) with Tin (II) 2-ethylhexanoate as a catalyst. These copolymers obtained were detected by 1H NMR, FT-IR, UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and automatic contact angle meter. The influences of the feed molar ratio of monomers, catalyst concentration, reaction time and reaction temperature, as well as microwave irradiation power on the copolymerization process were also studied. In vitro degradation tests indicated that these polycarbonate copolymers possess the slow degradation rates and strong hydrophobicity. In vitro release profiles of 5-Fu from copolymers showed that copolymers have the steady drug release rates and good controlled release properties.

Microwave-assisted Ring-Opening Polymerization of ε-Caprolactone in Presence of Hydrogen Phosphonates

Microwave-assisted Ring-Opening Polymerization of ɛ -Caprolactone in Presence of Hydrogen Phosphonates

Rapid synthesis of poly(trimethylene carbonate) by microwave-assisted ring-opening polymerization

Poly(trimethylene carbonate) (PTMC) was synthesized successfully by microwave-assisted ring-opening polymerization of trimethylene carbonate. The polymerizations were carried out in a single-mode microwave oven using ethylene glycol (EG) as the initiator in the absence of any metallic compound catalyst. The temperature–time profiles of the reaction mixture were investigated at different power levels and EG concentrations. The molar mass of the resulting PTMC and TMC monomer conversion by the microwave method is higher than those by the conventional method. Thermal properties of the resulting polymers were studied by differential scanning calorimetry. Microwave irradiation proved to be an effective and efficient method for the preparation of PTMC.