Biocompatible Polyester Research Articles

Binary Green Blends of Poly(lactic acid) with Poly(butylene adipate-co-butylene terephthalate) and Poly(butylene succinate-co-butylene adipate) and Their Nanocomposites.

Poly(lactic acid) (PLA) is the most widely produced biobased, biodegradable and biocompatible polyester. Despite many of its properties are similar to those of common petroleum-based polymers, some drawbacks limit its utilization, especially high brittleness and low toughness. To overcome these problems and improve the ductility and the impact resistance, PLA is often blended with other biobased and biodegradable polymers. For this purpose, poly(butylene adipate-co-butylene terephthalate) (PBAT) and poly(butylene succinate-co-butylene adipate) (PBSA) are very advantageous copolymers, because their toughness and elongation at break are complementary to those of PLA. Similar to PLA, both these copolymers are biodegradable and can be produced from annual renewable resources. This literature review aims to collect results on the mechanical, thermal and morphological properties of PLA/PBAT and PLA/PBSA blends, as binary blends with and without addition of coupling agents. The effect of different compatibilizers on the PLA/PBAT and PLA/PBSA blends properties is here elucidated, to highlight how the PLA toughness and ductility can be improved and tuned by using appropriate additives. In addition, the incorporation of solid nanoparticles to the PLA/PBAT and PLA/PBSA blends is discussed in detail, to demonstrate how the nanofillers can act as morphology stabilizers, and so improve the properties of these PLA-based formulations, especially mechanical performance, thermal stability and gas/vapor barrier properties. Key points about the biodegradation of the blends and the nanocomposites are presented, together with current applications of these novel green materials.

Recent advances on food waste pretreatment technology via microalgae for source of polyhydroxyalkanoates

Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polyester which are biosynthesized from the intracellular cells of microalgae through the cultivation of organic food waste medium. Before cultivation process, food waste must undergo several pre-treatment techniques such as chemical, biological, physical or mechanical in order to solubilize complex food waste matter into simpler micro- and macronutrients in which allow bio-valorisation of microalgae and food waste compound during the cultivation process. This work reviews four microalgae genera namely Chlamydomonas, Chlorella, Spirulina, and Botryococcus, are selected as suitable species due to rapid growth rate, minimal nutrient requirement, greater adaptability and flexibility prior to lower the overall production cost and maximized the production of PHAs. This study also focuses on the different mode of cultivation for the accumulation of PHAs followed by cell wall destabilization, extraction, and purification. Nonetheless, this review provides future insights into enhancing the productivity of bioplastic derived from microalgae towards low-cost, large-scale, and higher productivity of PHAs.

A 20-gauge active needle design with thin-film printed circuitry for interventional MRI at 0.55T.

This work aims to fabricate RF antenna components on metallic needle surfaces using biocompatible polyester tubing and conductive ink to develop an active interventional MRI needle for clinical use at 0.55 Tesla. A custom computer numeric control-based conductive ink printing method was developed. Based on electromagnetic simulation results, thin-film RF antennas were printed with conductive ink and used to fabricate a medical grade, 20-gauge (0.87 mm outer diameter), 90-mm long active interventional MRI needle. The MRI visibility performance of the active needle prototype was tested in vitro in 1 gel phantom and in vivo in 1 swine. A nearly identical active needle constructed using a 44 American Wire Gauge insulated copper wire-wound RF receiver antenna was a comparator. The RF-induced heating risk was evaluated in a gel phantom per American Society for Testing and Materials (ASTM) 2182-19. The active needle prototype with printed RF antenna was clearly visible both in vitro and in vivo under MRI. The maximum RF-induced temperature rise of prototypes with printed RF antenna and insulated copper wire antenna after a 3.96 W/kg, 15 min. long scan were 1.64°C and 8.21°C, respectively. The increase in needle diameter was 98 µm and 264 µm for prototypes with printed RF antenna and copper wire-wound antenna, respectively. The active needle prototype with conductive ink printed antenna provides distinct device visibility under MRI. Variations on the needle surface are mitigated compared to use of a 44 American Wire Gauge copper wire. RF-induced heating tests support device RF safety under MRI. The proposed method enables fabrication of small diameter active interventional MRI devices having complex geometries, something previously difficult using conventional methods.

Poly(butylene succinate) fibrous dressings containing natural antimicrobial agents

Poly(butylene succinate) (PBSU) is a biodegradable and biocompatible synthetic aliphatic polyester, which has been used extensively in packaging, catering and agriculture, and more recently in drug delivery and bone and cartilage repair. PBSU-based mats created by electrospinning show promise as wound dressing materials because of their good mechanical properties, high surface area-to-volume ratio and increased levels of porosity. In this work, we present the creation of antimicrobial PBSU fibrous mats through the incorporation of natural food grade agents via blend electrospinning. Three types of edible gums (namely arabic, karaya and tragacanth), two essential oils (coriander and lavender), and one free fatty acid (linoleic acid) were added to PBSU containing a chain extender and their effect on six clinically relevant pathogens was evaluated. Mats containing essential oils at the highest concentration studied (7% w/v) showed some antimicrobial behaviour against S. aureus, E. hirae and P. aeruginosa, whereas the incorporation of linoleic acid at both concentrations tested (3% and 5% w/v) gave a strong reaction against S. pyogenes. Gum arabic was the only gum that had a considerable impact on S. aureus. Furthermore, the three gums enhanced the mechanical properties of the polymer mats and brought them closer to those of the human skin, whilst all agents maintained the high biocompatibility of the PBSU mats when contacted with mouse fibroblasts. This work, for the first time, shows the great promise of PBSU blended fibres as a skin substitute and paves the way towards bioactive and cost effective wound dressings from renewable materials.

Effect of a small amount of poly(ethylene oxide) on crystal polymorphism of poly(l-lactic acid)

Poly(l-lactic acid) (PLLA) is a biodegradable and biocompatible polyester with great promise to be used in biomedical fields. Blending with poly(ethylene oxide) (PEO) can further improve the biocompatibility of PLLA. In this work, the effect of miscible blending of PEO on the crystal structure of PLLA was investigated. For neat PLLA, α′- and α-crystals are formed at crystallization temperature Tc < 110 °C and Tc ≥ 110 °C, respectively. With increasing PEO content, the difference of lattice spacing between α′- and α-crystals is gradually reduced. As PEO reaches 10 wt%, there is no apparent evidence of the presence of α′-crystal in the investigated Tc ranges. The blending effect of PEO on the crystal polymorphism of PLLA can be ascribed to the declined equilibrium melting point and lowered glass transition temperature.

Regenerated wool keratin-polybutylene succinate nanofibrous mats for drug delivery and cells culture

Keratin (Ker) protein regenerated from readily available and low-cost wastes (e.g. raw wool, feathers and textile by-products) is a promising natural polymer for tissue engineering and drug delivery.Nevertheless, while showing good bioactivity and great drug carrier properties, keratin lacks of suitable mechanical characteristics. To overcome this drawback, keratin was blended with poly(butylene succinate) (PBS), a biodegradable and biocompatible polyester able to confer mechanical integrity to the keratin based materials.Despite the poor compatibility at the molecular level between keratin and PBS, their 50-50 blends were successfully electrospun into manageable mats, made of randomly oriented nanofibers with mean diameter of 290 nm. Along with mechanical properties, PBS improves also the thermal stability of the keratin based nanofibrous mats. On the other hand, compared to PBS-only electrospun mats, the presence of keratin improves both swelling ability and biodegradability and amplifies the capacity of drug release as well as fibroblast proliferation of the blend mat.

Using biopolymer bodies for encapsulation of hydrophobic products in bacterium

Producing some small hydrophobic molecules in microbes is challenging. Often these molecules cannot cross membranes, and thus their production may be limited by lack of storage space in the producing organism. This study reports a new technology for in vivo storage of valuable hydrophobic products in/on biopolymer bodies in Escherichia coli. A biodegradable and biocompatible polyester – poly (3-hydroxybutyrate) (PHB) – was selected as the intracellular storage vessel to encapsulate lycopene, which is a chromogenic model compound. The hydrophobic interaction between lycopene and PHB was verified by using in vitro binding test and sucrose density gradient centrifugation. Further in vivo characterization was performed by using Confocal Laser Scanning Microscopy (CLSM). The images validated the in vivo co-localization between PHB granules and lycopene. The images also showed that lycopene aggregated in bacteria that did not produce PHB, which may challenge the commonly accepted hypothesis that most lycopene molecules are stored in cell membranes of recombinant host. We also confirmed that producing PHB did not negatively affect lycopene biosynthesis in the E. coli strains and collected data suggesting that PHB titer and lycopene titer were positively correlated when the cells were engineered to co-produce them. The biopolymers that encapsulated hydrophobic molecules could have many useful applications, especially in controlled release because the polymers are biodegradable, and the encapsulated products would be released during the polymer degradation.

The use of a synthetic shoulder patch for large and massive rotator cuff tears \u2013 a feasibility study

BackgroundThe aim of this study was to explore the feasibility of using a non-absorbable biocompatible polyester patch to augment open repair of massive rotator cuff tears (Patch group) and compare outcomes with other treatment options (Non-patch group).MethodsParticipants referred to orthopaedic clinics for rotator cuff surgery were recruited. Choice of intervention (Patch or Non-patch) was based on patient preference and intra-operative findings. Oxford Shoulder Score (OSS), Shoulder Pain and Disability Index (SPADI), and Constant score were completed at baseline and 6 months. Shoulder MRI was performed at baseline and 6 months to assess fat fraction and Goutallier classification pre- and post- treatment. Feasibility outcomes (including retention, consent and missing data) were assessed.ResultsSixty-eight participants (29 in the Patch group, 39 in Non-patch group) were included (mean age 65.3 years). Conversion to consent (92.6%), missing data (0% at baseline), and attrition rate (16%) were deemed successful feasibility endpoints. There was significant improvement in the Patch group compared to Non-patch at 6 months in OSS (difference in medians 9.76 (95% CI 2.25, 17.29) and SPADI: 22.97 (95% CI 3.02, 42.92), with no substantive differences in Constant score. The patch group had a higher proportion of participants improving greater than MCID for OSS (78% vs 62%) and SPADI (63% vs 50%) respectively. Analysis of the 48 paired MRIs demonstrated a slight increase in the fat fraction for supraspinatus (53 to 55%), and infraspinatus (26 to 29%) at 6 months. These differences were similar and in the same direction when the participants were analysed by treatment group. The Goutallier score remained the same or worsened one grade in both groups equally.ConclusionsThis study indicates that a definitive clinical trial investigating the use of a non-absorbable patch to augment repair of massive rotator cuff tears is feasible. In such patients, the patch has the potential to improve shoulder symptoms at 6 months.Trial registrationISRCTN, ISRCTN79844053, Registered 15th October 2014 (retrospectively registered).

Biodegradable poly(lactic acid) nanocomposites reinforced and toughened by carbon nanotubes/clay hybrids

Polylactic acid (PLA) is a biodegradable and biocompatible polyester derived from renewable resources like corn starch, presenting great potential in clinical applications like tissue engineering, implants and drug delivery systems. However, the intrinsic brittleness restricts its real applications. In this work, PLA nanocomposites were prepared by incorporating a small amount of carboxyl functionalized multi-walled carbon nanotubes (CNTs) and surface compatabilized montmorillonite (MMT) via technologies of freeze-drying and masterbatch-based melt blending. In the resulting nanocomposites, a well-distributed nano-filler network with microstructures of 1-D CNTs/2-D MMT platelets is formed favored by the enhanced interfacial interaction between the organic modified fillers with PLA matrix. Thanks to the well dispersed organic modified nanofillers, a large number of microcracks and extremely stretched PLA matrix are induced during tensile process, dissipating amounts of energy. As a result, the filler networks reinforce PLA with increment of 19% in modulus, remarkably increase by 13.8 times in toughness relative to PLA control without sacrificing strength. Thus, the PLA nanocomposites with excellent properties prepared through the facile and effective route possess broad prospect in biomedical applications.

Amino acid complexes with tin as a new class of catalysts with high reactivity and low toxicity towards biocompatible aliphatic polyesters

A series of complexes consisting of natural amino acids and tin (Sn(AA)2) prepared by conventional neutralization reactions were tested as a new class of cost-effective catalysts with high reactivity and low toxicity towards some biocompatible aliphatic polyesters. In our system, by using a simple catalyst and a benzyl alcohol (BnOH) initiator, biocompatible, and biodegradable aliphatic polyesters, such as poly(l-lactide), poly(e-caprolactone), and poly(trimethylene carbonate), were well prepared. The results demonstrated that Sn(AA)2 catalysts, especially the phenylalanine-tin complex (Sn(L-Phe)2) (Mn, up to 194 kg/mol), were suitable for the synthesis of moderate and high-molecular weight poly(l-lactide), which exhibited good biocompatibility. Analysis of the backbone structure and end groups of low-molar-mass polymers by using MALDI-TOF mass spectra and 1H NMR spectroscopy suggested that the reaction proceeds by a dual activation mechanism. Given their low cost, simple preparation, high reactivity, and low toxicity, complexes consisting of natural amino acids and tin are promising for industrial-scale production of biocompatible aliphatic polyesters. A series of complexes consisting of natural amino acids and tin were developed as a new class of cost-effective catalysts with high reactivity and low toxicity towards some biocompatible aliphatic polyesters. The results demonstrated that Sn(AA)2 catalysts, especially the phenylalanine-tin complex (Sn(L-Phe)2) (Mn, up to 194 kg/mol), were suitable for the synthesis of moderate- and high-molecular-weight poly(L-lactide), which exhibited good biocompatibility.

Co-Networks Poly(hydroxyalkanoates)-Terpenes to Enhance Antibacterial Properties.

Biocompatible and biodegradable bacterial polyesters, poly(hydroxyalkanoates) (PHAs), were combined with linalool, a well-known monoterpene, extracted from spice plants to design novel antibacterial materials. Their chemical association by a photo-induced thiol-ene reaction provided materials having both high mechanical resistance and flexibility. The influence of the nature of the crosslinking agent and the weight ratio of linalool on the thermo-mechanical performances were carefully evaluated. The elongation at break increases from 7% for the native PHA to 40% for PHA–linalool co-networks using a tetrafunctional cross-linking agent. The materials highlighted tremendous anti-adherence properties against Escherichia coli and Staphylococcus aureus by increasing linalool ratios. A significant decrease in antibacterial adhesion of 63% and 82% was observed for E. coli and S. aureus, respectively.

A Molecular Dynamics Study on Polycaprolactone -Metal Oxide Interactions

In order to realize the macroscopic features of a number of chemically bonded multi-layer dielectric and composite materials, interactions of metal oxide surfaces, polymer surface atoms, and near-surface atoms are very beneficial. The simulation study of polymer-metal oxides interfaces is of great importance in investigating the adhesion and miscibility features of these systems that are inherently challenging to obtain experimentally or for which there is no experimental data, even if some low data exist, they are not reliable. Polycaprolactone (PCL) is biocompatible, biodegradable, non-toxic and hydrophobic polyester that has been used in tissue engineering, such as a bioactive implant. Hence, the molecular dynamics simulations of PCL are carried out to investigate its surface interaction with metal oxides as ZnO, CuO, Fe2O3, NiO and SiO2. The force field of COMPASS is applied to simulations in order to compute interfacial and solubility parameters. Molecular dynamics approach to investigate the interaction and adsorption manner of PCL with metal oxides. Whereas investigations are useful in exploring polymer composites. Much better adhesion is achieved by the calculations between the PCL oligomer and the metal oxides under investigation. The negative values of interaction energy have to be forecasted despite the presence of acid-base or hydrogen-bonding interactions.

Functional Polymers and Polymeric Materials From Renewable Alpha-Unsaturated Gamma-Butyrolactones.

Sustainable chemistry requires application of green processes and often starting materials originate from renewable resources. Biomass-derived monomers based on five-membered γ-butyrolactone ring represent suitable candidates to replace sources of fossil origin. α-Methylene-γ-butyrolactone, β-hydroxy-α-methylene-γ-butyrolactone, and β- and γ-methyl-α-methylene-γ-butyrolactones bearing exocyclic double bond are available directly by isolation from plants or derived from itaconic or levulinic acids available from biomass feedstock. Exocyclic double bond with structural similarity with methacrylates is highly reactive in chain-growth polymerization. Reaction involves the linking of monomer molecules through vinyl double bonds in the presence of initiators typical for radical, anionic, zwitterionic, group-transfer, organocatalytic, and coordination polymerizations. The formed polymers containing pendant ring are characterized by high glass transition temperature (Tg > 195°C) and render decent heat, weathering, scratch, and solvent resistance. The monomers can also be hydrolyzed to open the lactone ring and form water-soluble monomers. Subsequent radical copolymerization in the presence of cross-linker can yield to hydrogels with superior degree of swelling and highly tunable characteristics, depending on the external stimuli. The five-membered lactone ring allows copolymerization of these compounds by ring opening polymerization to provide polyesters with preserved methylene functionality. In addition, both the lactone ring and the methylene double bond can be attacked by amines. Polyaddition with di- or multi-amines leads to functional poly(amidoamines) with properties tunable by structure of the amines. In this mini-review, we summarize the synthetic procedures for preparation of polymeric materials with interesting properties, including thermoplastic elastomers, acrylic latexes, stimuli-sensitive superabsorbent hydrogels, functional biocompatible polyesters, and poly(amidoamines).

Recent Advances in Metal-Mediated Stereoselective Ring-Opening Polymerization of Functional Cyclic Esters towards Well-Defined Poly(hydroxy acid)s: From Stereoselectivity to Sequence-Control.

Poly(hydroxy acid)s are a family of biocompatible and (bio)degradable polyesters with various outcomes in different domains of application. To date, poly(hydroxy acid)s are best prepared by ring-opening polymerization (ROP) of the corresponding cyclic esters. Using racemic chiral monomers featuring side-chain groups enables to access, providing a stereoselective catalyst/initiator system is implemented, stereoregular functional polymers, thereby improving their physico-chemical properties, and ultimately, widening their range of uses. Here, we highlight a few important advances in metal-mediated stereoselective ROP of cyclic esters towards the synthesis of (functional) stereoregular poly(hydroxy acid)s that have recently been disclosed, emphasizing on (functional) β- and γ-lactones, diolide and O-carboxyanhydride (OCA) monomers and yttrium-based catalysis. Fine-tuning of the substituents flanked on the catalyst ligand enables reaching poly(hydroxy acid)s with syndiotactic and also isotactic microstructures. The stereocontrol mechanisms at work and their probable origin, relying on steric but also electronic factors imparted in particular by the ligand substituents, are discussed. Taking advantage of such stereoselective ROPs, original copoly(hydroxy acid)s with gradient or alternated patterns then become accessible from the use of mixtures of chemically different, oppositely configured enantiopure monomers.

Modeling the release of curcumin from microparticles of poly(hydroxybutyrate) [PHB

Polyhydroxybutyrate (PHB) is biodegradable and biocompatible polyester that has been recently used for developing different drug delivery systems (DDS). Microspheres as DDS, consist of a polymeric matrix with a diameter of 1–125 μm which contains a substance entrapped, and then released mainly through diffusion. In order to make DDS viable for commercial applications, it is essential to develop models that describe and predict the substance release kinetic. In this study, microspheres of PHB with curcumin entrapped were synthesized; the release of curcumin was studied and modeled. As a first approach, a physical model was introduced, in which mass transference was considered analogous to heat transference. The proposed model was based on local mass balance through the classical diffusion equation and total mass balance imposed through an integro-differential equation. The total mass balance introduced nonlinearities in the dynamics of the drug within the fluid; therefore, a semi-analytical approach based on the heat balance integral method was applied to solve the proposed model. Finally, by using the experimental rate of release of curcumin, the semi-analytical solutions to the proposed model were compared with the experimental release data, showing the importance of adding mass balance in the nonlinear mathematical model in order to describe more accurately the release kinetics.

Crosslinking of Electrospun Fibres from Unsaturated Polyesters by Bis-Triazolinediones (TAD).

Crosslinking of an unsaturated aliphatic polyester poly(globalide) (PGl) by bistriazolinediones (bisTADs) is reported. First, a monofunctional model compound, phenyl–TAD (PTAD), was tested for PGl functionalisation. 1H-NMR showed that PTAD–ene reaction was highly efficient with conversions up to 97%. Subsequently, hexamethylene bisTAD (HM–bisTAD) and methylene diphenyl bisTAD (MDP–bisTAD) were used to crosslink electrospun PGl fibres via one- and two-step approaches. In the one-step approach, PGl fibres were collected in a bisTAD solution for in situ crosslinking, which resulted in incomplete crosslinking. In the two-step approach, a light crosslinking of fibres was first achieved in a PGl non-solvent. Subsequent incubation in a fibre swelling bisTAD solution resulted in fully amorphous crosslinked fibres. SEM analysis revealed that the fibres’ morphology was uncompromised by the crosslinking. A significant increase of tensile strength from 0.3 ± 0.08 MPa to 2.7 ± 0.8 MPa and 3.9 ± 0.5 MPa was observed when PGI fibres were crosslinked by HM–bisTAD and MDP–bisTAD, respectively. The reported methodology allows the design of electrospun fibres from biocompatible polyesters and the modulation of their mechanical and thermal properties. It also opens future opportunities for drug delivery applications by selected drug loading.

Pyridyl-urea catalysts for the solvent-free ring-opening polymerization of lactones and trimethylene carbonate

The ring-opening polymerization (ROP) of lactones is an effective method for the preparation of biocompatible and biodegradable aliphatic polyesters, for which the development of efficient organocatalysts with high activity and good controllability is highly desirable. A series of novel pyridyl-urea catalysts has been synthesized and applied in the solvent-free ROP of lactones and trimethylene carbonate. Combined with 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), the pyridyl-urea/MTBD systems showed a fast and living/controlled behavior in the ROP, generating polymers with narrow molecular weight distributions. The influences of catalyst structure, type of base, pyridyl-urea/base ratio, feed ratio of monomer/initiator and reaction temperature on the catalytic properties were investigated. A possible mechanism was proposed on the basis of NMR titration and dilution experiments.

Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy.

The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment.

Targeted delivery of poly (methyl methacrylate) particles in colon cancer cells selectively attenuates cancer cell proliferation

Poly (methyl methacrylate) (PMMA) is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and the most important characteristics of PMMA is that it does not produce any toxicity. There is not much information about PMMA action on the colon cancer cells. In the present study, we have synthesized PMMA nanoparticles. The distribution pattern of PMMA particles was analysed by Zeta sizer and the size of the particles was calculated by using quasi elastic light scattering (QELS). The surface structure and the morphology of PMMA were characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM), respectively. We have also analysed their effects on cancerous cells (human colorectal carcinoma cells, HCT-116) and normal, healthy cells (human embryonic kidney cells, HEK-293) by using morphometric, MTT, DAPI and wound healing methods. We report that PMMA particles inhibited the cancer cell viability in a dose-dependent manner. The lower dose (1.0 μg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 μg/ml, 5.0 μg/mL and 7.5 μg/mL) showed steadily decrease in the cancer cell viability. We also report that PMMA is highly selective to cancerous cells (HCT-116), as we did not find any action on the normal healthy cells (HEK-293). In conclusion, our results suggest PMMA particles are potential biomaterials to be used in the treatment of colon cancer.

Facile Synthesis and Properties of Multifunctionalized Polyesters by Passerini Reaction as Thermosensitive, Biocompatible, and Triggerable Drug Release Carriers.

We developed a facile synthesis for a series of multifunctionalized polyesters by Passerini three-component polymerization (Passerini-3CP) in a "one-pot" method at room temperature using serial dicarboxylic acids, dialdehyde, and tert-butyl isocyanide as monomers. First, the effects of monomer feed ratio, monomer concentration, and different dicarboxylic acids involved in the polymerization were systematically investigated. The in situ FTIR and GPC measurements have suggested a step-growth mechanism for Passerini-3CP. Second, five succinic acid end-capped polyethylene glycols (S-PEGs) with different molecular weights of 400, 800, 1000, 2000, and 4000 g/mol were prepared and selected as dicarboxylic acids for the subsequent Passerini-3CP to fabricate the thermosensitive and biocompatible polyesters. Among the five resulting polyesters, four polyesters from S-PEG-400, S-PEG-800, S-PEG-1000, and S-PEG-2000 show reversible response to the external temperature, and the lower critical solution temperature (LCST) in water is in the range of 28.5-84.2 °C. Through the copolymerization of S-PEG-400 and S-PEG-800, the LCSTs for functional polyesters can be conveniently controlled to be 38.7, 42.3, and 58.0 °C, respectively. After 24-72 h of incubation in polyester solution, the viability rate of HeLa cells reached up to 80-107%, showing its excellent biocompatibility. The cleavable polyesters were also prepared by integrating S-S bonds onto their backbones in Passerini-3CP of 3,3'-dithiodipropionic acid as one comonomer for the biomedical applications. With the aid of the hydrophobicity of doxorubicin (DOX) and thermosensitivity of polyesters, the doxorubicin-loaded carriers with the size of 200-400 nm and core-shell structure were easily obtained by dialysis below LCST and subsequent heating to LCST. The effective release of DOX from the carriers can be triggered by the characteristic reaction of l-glutathione (GSH) with S-S bonds in the functionalized polyester backbones.