Search Results (18)

The development of hydrophilic biodegradable polymers is crucial for a range of biomedical applications, including targeted drug delivery and prosthetics. Ring-opening polymerization of substituted ε-caprolactone monomers provides an efficient method for the synthesis of polyesters with tailored properties. In this work, a synthetic approach for the preparation of ester- and morpholinoamido-disubstituted ε-caprolactone monomers was developed. Poorly defined polymers were obtained from the monomers, bearing two ester groups due to the competitive transesterification of the pendant substituents. On the other hand, the disubstituted morpholinoamido-ε-caprolactone was polymerized in a controlled manner by ring-opening polymerization, and amorphous homopolymers with a high glass transition temperature (112 °C) and good solubility in water were obtained. Statistical and block copolymers with the unsubstituted ε-caprolactone were also prepared, and DLS analysis of the amphiphilic block copolymers in water shows the presence of self-assembled particles. These results demonstrate the potential of morpholinoamido-functionalized ε-caprolactone derivatives as building blocks for the development of biodegradable polymeric materials for biomedical applications. Full article

To prepare novel biodegradable copolymers with functional substituents that are distributed statistically or randomly over the macromolecule chain and have improved characteristics compared to homopolymers, we conducted a series of synthetic experiments with a novel cyclic monomer, 5-(benzyloxy)-1,3-dioxepan-2-one (4). This compound was synthesized, and its homopolymer, as well as its copolymers with L-lactide, ε-caprolactone and trimethylene carbonate, were prepared in a polymerization solution with stannous octoate as the initiator. The formation of the copolymers was confirmed using NMR spectroscopy and DSC data. The distribution of the monomeric units of the substituted 7CC in the copolymers with L-lactide and ε-caprolactone is random, as it is close to a statistical distribution. The copolymer with TMC is a gradient copolymer due to the different rates of monomer polymerization. The copolymer with a composition of 10(ε-CL):1(carbonate 4) can be considered a promising polymer after the deprotection of the hydroxy group for the inoculation of the functional substituents due to its convenience of preparation and properties similar to those of poly(ε-caprolactone). Full article

A new aluminum complex (NSO)AlMe₂ featuring a hydrogen bond donor on the ligand backbone has been synthesized via the reaction of AlMe₃ with 1-((2-(isopropylamino)phenyl)thio)propan-2-ol (NSO-H) and spectroscopically characterized. In the complex, the aluminum atom is in a distorted tetrahedral coordination sphere determined by the anionic oxygen and neutral nitrogen atoms of the ligand and by the two carbon atoms of the alkyl groups. After proper activation, the complex (NSO)AlMe₂ was able to promote the ring-opening polymerization of L-, rac-lactide, ε-caprolactone and rac-β-butyrolactone. The polymerization of rac-lactide was faster than that of L-lactide: in a toluene solution at 80 °C, the high monomer conversion of 100 equivalents was achieved in 1.5 h, reaching a turnover frequency of 63 mol_LA·mol_Al^–1·h^–1. The experimental molecular weights of the obtained polymers were close to those calculated, assuming the growth of one polymer chain for one added alcohol equivalent and the polydispersity indexes were monomodal and narrow. The kinetic investigation of the polymerization led to the determination of the apparent propagation constants and the Gibbs free energies of activation for the reaction; the terminal groups of the polymers were also identified. The complex (NSO)AlMe₂ was active in harsh conditions such as at a very low concentration or in the melt using technical-grade rac-lactide. A relatively high level of activity was observed in the ring-opening polymerization of ε-caprolactone and rac-β-butyrolactone. DFT calculations were performed and revealed the central role of the NH function of the coordinated ligand. Acting as a hydrogen bond donor, it docks the monomer in the proximity of the metal center and activates it toward the nucleophilic attack of the growing polymer chain. Full article

Poly(L-lactic acid) (PLLA) and poly(ε-caprolactone) (PCL), two biodegradable and biocompatible polymers that are commonly used for biomedical applications, are, respectively, the result of the ring-opening polymerization of LA and ε-CL, cyclic esters, which can be produced according to several mechanisms (cationic, monomer-activated cationic, anionic, and coordination-insertion), except for L-lactide, which is polymerized only by anionic, cationic, or coordination-insertion polymerization. A series of well-defined PLLA-b-PCL block copolymers have been obtained starting from the same PLLA homopolymer, having a molar mass of 2500 g·mol⁻¹, and being synthesized by coordination-insertion in the presence of tin octoate. PCL blocks were obtained via a cationic-activated monomer mechanism to limit transesterification reactions, and their molar masses varied from 1800 to 18,500 g·mol⁻¹. The physicochemical properties of the copolymers were determined by ¹H NMR, SEC, and DSC. Moreover, a series of nanoparticles (NPs) were prepared starting from these polyester-based copolymers by an emulsification/evaporation method. The sizes of the obtained NPs varied between 140 and 150 nm, as a function of the molar mass of the copolymers. Monomodal distribution curves with PDI values under 0.1 were obtained by Dynamic Light Scattering (DLS) and their spherical shape was confirmed by TEM. The increase in the temperature from 25 to 37 °C induced only a very slight decrease in the NP sizes. The results obtained in this preliminary study indicate that NPs have a temperature stability, allowing us to consider their use as drug-loaded nanocarriers for biomedical applications. Full article

Many therapies require the transport of therapeutic compounds or substances encapsulated in carriers that reduce or, if possible, eliminate their direct contact with healthy tissue and components of the immune system, which may react to them as something foreign and dangerous to the patient’s body. To date, inorganic nanoparticles, solid lipids, micelles and micellar aggregates, liposomes, polymeric micelles, and other polymer assemblies were tested as drug carriers. Specifically, using polymers creates a variety of options to prepare nanocarriers tailored to the chosen needs. Among polymers, aliphatic polyesters are a particularly important group. The review discusses controlled synthesis of poly(β-butyrolactone)s, polylactides, polyglycolide, poly(ε-caprolactone), and copolymers containing polymacrolactone units with double bonds suitable for preparation of functionalized nanoparticles. Discussed are syntheses of aliphatic polymers with controlled molar masses ranging from a few thousand to 10⁶ and, in the case of polyesters with chiral centers in the chains, with controlled microstructure. The review presents also a collection of methods useful for the preparation of the drug-loaded nanocarriers: classical, developed and mastered more recently (e.g., nanoprecipitation), and forgotten but still with great potential (by the direct synthesis of the drug-loaded nanoparticles in the process comprising monomer and drug). The article describes also in-vitro and model in-vivo studies for the brain-targeted drugs based on polyester-containing nanocarriers and presents a brief update on the clinical studies and the polyester nanocarrier formulation approved for application in the clinics in South Korea for the treatment of breast, lung, and ovarian cancers. Full article

In this study, we investigated the influence of γ-irradiation (0, 50, and 100 kGy) doses on the chemical and mechanical properties of biodegradable poly(hydroxybutyrate-valerate)/poly(caprolactone) (PHBV/PCL) polymer blends rich in low-molar-mass PCL, which were prepared using a co-rotating twin-screw extruder. In parallel, the density functional theory (DFT) and the time-dependent DFT (TD-DFT) methods were used together with a model containing four monomer units to provide an insight into the electronic structure, chemical bonds, and spectroscopic (such as Nuclear Magnetic Resonance (NMR) and Ultraviolet-visible (UV-vis)) properties of PHBV and PCL blend phases, which are critical for predicting and designing new materials with desired properties. We found that an increase in γ-irradiation doses caused splitting instead of crosslinks in the polymer chains, which led to evident deformation and an increase in tensile strength at break of 2.0 to 5.7 MPa for the PHBV/PCL blend. Further, this led to a decrease in crystallinity and proved the occurrence of a more favorable interaction between the blend phases. Full article

In this work, thioether-amide ligands featuring a combination of hard amide groups with soft donor groups have been employed to develop new zinc catalysts for the ring-opening polymerization of cyclic esters. All complexes were prepared in high yields through alkane elimination reactions with diethyl zinc and characterized using nuclear magnetic resonance (NMR) spectroscopy. Density functional theory (DFT) characterization provided insight into the parameters that influence catalytic activity, such as steric hindrance at the metal center, Lewis acidity and electronic density of thioether-amide ligands. In the presence of one equivalent of isopropanol, all complexes were active in the ring-opening polymerization of rac-β-butyrolactone. Quantitative conversion of 100 monomer equivalents was achieved within 1 h at 80 °C in a toluene solution. Number-average molecular weights increased linearly with monomer conversion; the values were in optimal agreement with those expected, and polydispersity index values were narrow and relatively constant throughout the course of polymerization. The most active complex was also effective in the ring-opening polymerization of ε-caprolactone and L-lactide. To propose a reliable reaction path, DFT calculations were undertaken. In the first step of the reaction, the acidic proton of the alcohol is transferred to the basic nitrogen atom of the amide ligand coordinated to the zinc ion. This leads to the alcoholysis of the Zn-N bond and the formation of an alcoholate derivative that starts the polymerization. In subsequent steps, the reaction follows the classical coordination–insertion mechanism. Full article

Syntheses of novel bifunctional poly(methyl methacrylate) (PMMA)-, poly(styrene) (PS)-, and (poly ε-caprolactone) (PCL)-based atom transfer radical polymerization (ATRP) macroinitiators derived from p-xylene-bis(1-hydroxy-3-thia-propanoloxy) core were carried out to obtain ABA-type block copolymers. Firstly, a novel bifunctional ATRP initiator, 1,4-phenylenebis(methylene-thioethane-2,1-diyl)bis(2-bromo-2-methylpropanoat) (PXTBR), synthesized the reaction of p-xylene-bis(1-hydroxy-3-thia-propane) (PXTOH) with α-bromoisobutryl bromide. The PMMA and PS macroinitiators were prepared by ATRP of methyl methacrylate (MMA) and styrene (S) as monomers using (PXTBR) as the initiator and copper(I) bromide/N,N,N′,N″,N″-pentamethyldiethylenetriamine (CuBr/PMDETA) as a catalyst system. Secondly, di(α-bromoester) end-functionalized PCL–based ATRP macronitiator (PXTPCLBr) was prepared by esterification of hydroxyl end groups of PCL-diol (PXTPCLOH) synthesized by Sn(Oct)₂–catalyzed ring opening polymerization (ROP) of ε-CL in bulk using (PXTOH) as initiator. Finally, ABA-type block copolymers, PXT(PS-b-PMMA-b-PS), PXT(PMMA-b-PS-b-PMMA), PXT(PS-b-PCL-b-PS), and PXT(PMMA-b-PCL-b-PMMA), were synthesized by ATRP of MMA and S as monomers using PMMA-, PS-, and PCL-based macroinitiators in the presence of CuBr/PMDETA as the catalyst system in toluene or N,N-dimethylformamide (DMF) at different temperatures. In addition, the extraction abilities of PCL and PS were investigated under liquid–liquid phase conditions using heavy metal picrates (Ag⁺, Cd²⁺, Cu²⁺, Hg²⁺, Pb²⁺, and Zn²⁺) as substrates and measuring with UV-Vis the amounts of picrate in the 1,2–dichloroethane phase before and after treatment with the polymers. The extraction affinity of PXTPCL and PXTPS for Hg²⁺ was found to be highest in the liquid–liquid phase extraction experiments. Characterizations of the molecular structures for synthesized novel initiators, macroinitiators, and the block copolymers were made by spectroscopic (FT–IR, ESI–MS, ¹H NMR, ¹³C NMR), DSC, TGA, chromatographic (GPC), and morphologic SEM. Full article

Poly(ε-Caprolactone)s are biodegradable and biocompatible polyesters that have gained considerable attention for drug delivery applications due to their slow degradation and ease of functionalization. One of the significant advantages of polycaprolactone is its ability to attach various functionalities to its backbone, which is commonly accomplished through ring-opening polymerization (ROP) of functionalized caprolactone monomer. In this review, we aim to summarize some of the most recent advances in polycaprolactones and their potential application in drug delivery. We will discuss different types of polycaprolactone-based drug delivery systems and their behavior in response to different stimuli, their ability to target specific locations, morphology, as well as their drug loading and release capabilities. Full article

A highly efficient one-step approach to the macromonomer synthesis using modified aluminum complexes as catalysts of ring-opening polymerization (ROP) of ε-caprolactone and D,L-lactide was developed. The syntheses, structures, and catalytic activities of a wide range of aluminum salen complexes, 3a-c, functionalized with unsaturated alcohol (HO(CH₂)₄OCH=CH₂) are reported. X-Ray diffraction studies revealed a tetragonal pyramidal structure for 3c. Among the complexes 3a-c, the highest activity in bulk ROP of ε-caprolactone and D,L-lactide was displayed by 3b, affording polyesters with controlled molecular weights at low monomer to initiator ratios (M_n up to 15,000 g mol⁻¹), relatively high polydispersities (Ð~1.8) and high number-average functionalities (F_n up to 85%). Full article

A series of heterogeneous Zn-Co double metal cyanide (DMC) catalysts were investigated for ring-opening polymerization (ROP) of various cyclic monomers. Notably, inexpensive and commonly used organic solvents such as acetone, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, and 1-methylpyrrolidin-2-one were very effective complexing agents for the preparation of DMC catalysts, showing high catalytic activity for the ROP of propylene oxide, ε-caprolactone, and δ-valerolactone. The chemical structures and compositions of the resultant catalysts were determined using various techniques such as FT-IR, X-ray photoelectron spectroscopy, powder X-ray diffraction, and elemental analysis. α,ω-Hydroxyl-functionalized polyether and polyester polyols with high yields and tunable molecular weights were synthesized in the presence of various initiators to control functionality. Kinetic studies of the ROP of δ-valerolactone were also performed to confirm the reaction mechanism. Full article

Catalytic ring-opening polymerization (ROP) of cyclic esters (lactides, lactones) and cyclic ethylene phosphates is an effective way to process materials with regulated hydrophilicity and controlled biodegradability. Random copolymers of cyclic monomers of different chemical nature are highly attractive due to their high variability of characteristics. Aryloxy-alkoxy complexes of non-toxic metals such as derivatives of 2,6-di-tert-butyl-4-methylphenoxy magnesium (BHT-Mg) complexes are effective coordination catalysts for homopolymerization of all types of traditional ROP monomers. In the present paper, we report the results of density functional theory (DFT) modeling of BHT-Mg-catalyzed copolymerization for lactone/lactide, lactone/ethylene phosphate and lactide/ethylene phosphate mixtures. ε-Caprolactone (ε-CL), l-lactide (l-LA) and methyl ethylene phosphate (MeOEP) were used as examples of monomers in DFT simulations by the Gaussian-09 program package with the B3PW91/DGTZVP basis set. Both binuclear and mononuclear reaction mechanistic concepts have been applied for the calculations of the reaction profiles. The results of calculations predict the possibility of the formation of random copolymers based on l-LA/MeOEP, and substantial hindrance of copolymerization for ε-CL/l-LA and ε-CL/MeOEP pairs. From the mechanistic point of view, the formation of highly stable five-membered chelate by the products of l-LA ring-opening and high donor properties of phosphates are the key factors that rule the reactions. The results of DFT modeling have been confirmed by copolymerization experiments. Full article

To achieve a high stability in physiological environment and rapid intracellular drug release, a biodegradable zwitterionic triblock copolymer with a disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCBMA-SS-PCL-SS-PCBMA) was prepared for micellar carrier to delivery doxorubicin (DOX) into tumor cells. PCBMA-SS-PCL-SS-PCBMA was obtained by following steps: i) introducing disulfide bonds through end-group modification of PCL diol with cystamine dihydrochloride; ii) preparing PCL-RAFT macromolecular chain transfer agent by EDC/NHS chemistry; iii) RAFT polymerization of zwitterionic monomer. Self-assembling from PCBMA-SS-PCL-SS-PCBMA, polymeric micelles had many advantages, such as ultra-low protein absorption in serum and obvious reduction-responsiveness in the presence of DTT. Furthermore, DOX-loaded micelles exhibited high stability upon centrifugation and lyophilization, a fast intracellular drug release and enhanced drug efficacy due to GSH-triggered PCBMA shell shedding and micellar reassembling. Thus, the polymeric micelles integrated several functions and properties could be prospectively utilized as valuable nanocarriers in cancer chemotherapeutics. Full article

The present work studies the functional behavior of novel poly(ε-caprolactone) (PCL) membranes functionalized with reduced graphene oxide (rGO) nanoplatelets under simulated in vitro culture conditions (phosphate buffer solution (PBS) at 37 °C) during 1 year, in order to elucidate their applicability as scaffolds for in vitro neural regeneration. The morphological, chemical, and DSC results demonstrated that high internal porosity of the membranes facilitated water permeation and procured an accelerated hydrolytic degradation throughout the bulk pathway. Therefore, similar molecular weight reduction, from 80 kDa to 33 kDa for the control PCL, and to 27 kDa for PCL/rGO membranes, at the end of the study, was observed. After 1 year of hydrolytic degradation, though monomers coming from the hydrolytic cleavage of PCL diffused towards the PBS medium, the pH was barely affected, and the rGO nanoplatelets mainly remained in the membranes which envisaged low cytotoxic effect. On the other hand, the presence of rGO nanomaterials accelerated the loss of mechanical stability of the membranes. However, it is envisioned that the gradual degradation of the PCL/rGO membranes could facilitate cells infiltration, interconnectivity, and tissue formation. Full article

ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies were tested, a first one with direct polymerization of CL with the native amino acids and a second one involving the use of an amino acid with protected functional groups. The first route showed that mainly polycaprolactone (PCL) homopolymer could be obtained and highlighted the lack of reactivity of the unmodified amino acids due to poor solubility and affinity with the lipase active site. The second strategy based on protected cysteine showed higher monomer conversion, with the amino acids acting as (co-)initiators, but their insertion along the PCL chains remained limited to chain endcapping. These results thus showed the possibility to synthesize enzymatically polycaprolactone-based chains bearing amino acids units. Such cysteine endcapped PCL materials could then find application in the biomedical field. Indeed, subsequent functionalization of these polyesters with drugs or bioactive molecules can be obtained, by derivatization of the amino acids, after removal of the protecting group. Full article