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In this study, we report the acid-catalyzed and high pressure assisted ring-opening polymerization (ROP) of g-butyrolactone (GBL). The use of a dually-catalyzed approach combining an external physical factor and internal catalyst (trifluoromethanesulfonic acid (TfOH) or p-toluenesulfonic acid (PTSA)) enforced ROP of GBL, which is considered as hardly polymerizable monomer still remaining a challenge for the modern polymer chemistry. The experiments performed at various thermodynamic conditions (T ¼ 278–323 K and p ¼ 700–1500 MPa) clearly showed that the high pressure supported polymerization process led to obtaining well-defined macromolecules of better parameters (Mn ¼ 2200–9700 g mol 1; Đ ¼ 1.05–1.46) than those previously reported. Furthermore, the parabolic-like dependence of both the molecular weight (MW) and the yield of obtained polymers on variation in temperature and pressure at either isobaric or isothermal conditions was also noticed, allowing the determination of optimal conditions for the polymerization process. However, most importantly, this strategy allowed to significantly reduce the reaction time (just 3 h at room temperature) and increase the yield of obtained polymers (up to 0.62 gPGBL/gGBL). Moreover, despite using a strongly acidic catalyst, synthesized polymers remained non-toxic and biocompatible, as proven by the cytotoxicity test we performed in further analysis. Additional investigation (including MALDI-TOF measurements) showed that the catalyst selection affected not only MW and yield but also the linear/cyclic form content in obtained macromolecules. These findings show the way to tune the properties of PGBL and obtain polymer suitable for application in the biomedical industry.

Novel polymer networks composed of biocompatible, hydrophilic poly(2-isopropenyl-2-oxazoline) (PiPOx), poly(ethylene oxide) (PEO), and selected biologically active compounds (cinnamic acid, benzoic acid or eugenol) were developed for potential antimicrobial applications. The applied crosslinking method, based on the addition reaction between oxazoline pendant groups and chosen reagents containing carboxyl functions, is relatively facile, free from by-products, and thus well suited for biomaterial preparation. The one-step synthesis enabled efficient network formation with high gel contents (>90%). The chemical structure of the newly synthesized networks was characterized using Fourier Transform Infrared-attenuated Total Reflection spectroscopy (FTIR-ATR) and 13C Magic-Angle Spinning (MAS) NMR. To evaluate the suitability for biomedical applications, swelling in water and the mechanical properties of the networks were investigated. The antimicrobial efficacy of the prepared hydrogels was tested in neutral medium both by the agar diffusion method and in the liquid culture against Gram-positive and Gram-negative strains: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloaceae. All the tested hydrogels showed an antimicrobial effect in the direct contact zone. Moreover, the eugenol loaded hydrogel expressed a broader bacteriostatic effect inhibiting microorganism growth beyond the contact zone. These form-stable hydrogels with antibacterial properties may be of interest for designing materials dedicated to biomedical applications.

The syntheses, properties and selected applications of star-shaped polymers with arms composed of homo- or copolymers of polylactide (PLA) is reviewed. The star-shaped (including miktoarm stars), dendritic, and branched polymers with a specified or varying numbers of arms were synthesized depending on the applied core molecule. Examples of a large number of various structures of star-shaped PLA polymers are precisely described. The growing interest in the synthesis of star-shaped and branched PLAs is primarily motivated by their potential applications in the biomedical and pharmaceutical areas. Therefore, the thermal, rheological, and mechanical properties, as well as various applications, of PLA stars as, for example, drug carriers, medical materials, and components of hydrogels, are also reported.

In this study, the stereocomplexation of poly- l -lactide (PLLA) and poly- d -lactide (PDLA) was monitored in real time using fluorescence spectroscopy. To introduce fluorescence probes at the beginning (i.e., α position) of the PLLA and PDLA chains, a pyrene derivative was employed as an initiator for ring-opening polymerization of l,l -lactide (LLA) and d,d -lactide (DLA), respectively, and the post-polymerization functionalization of the hydroxyl end-groups of the PLLA were obtained by initiating LLA using the BuOH/Sn(Oct)2 system to form polylactide decorated with a pyrene moiety on the opposite polymer chain-end (i.e., ω position). Using these approaches, linear Py-PLLA-OH, Py-PDLA-OH, and Bu-PLLA-Py with molar masses equal to 3100, 3350 and 3300 g mol−1, respectively, were prepared. Next, equimolar compositions of Py-PLLA-OH/Py-PDLA-OH and Py-PDLA-OH/Bu-PLLA-Py in different solvents were prepared, and the stereocomplexation, which is related to excimer formation between the Py end-groups, was directly observed using fluorescence measurements of the excimer emission at 470 nm in both AcCN and THF solutions, respectively. The kinetic curves based on the IE/IM ratio as a function of time are complex in shape and indicate interaction of two enantiomeric chains occurred. In addition, at the beginning of the association, the PLA enantiomeric pairs form stereocomplex crystallites. The probability of parallel and antiparallel interactions of PLA enantiomers during stereocomplexation is similar and consistent with Cantow's calculations. In addition, the DSC analysis of the final PLA products confirmed that only stereocomplex crystallites were formed in these two solvents.

In this paper a set of linear and star -shaped polylactides (PLA's) containing a different number of -OH end-groups (1, 2, 4, 6 and 8) were synthesized. To compare the extent of interactions between different end-groups, the OH end-groups were transformed to COOH end-groups. To attain the proper conditions of this transformation, the conditions were optimized for the chosen model and then used for all synthesized polymers. The structure of synthesized polymers were confirmed by SEC-MALS, NMR and ATR FT-IR analyses. It was shown that PLA's architecture and number of OH and COOH groups in a single macromolecule have an influence on a viscosity of their solution due to their self-organization. For star -shaped PLA's containing higher than four number of COOH end-groups, it has been observed for the first time that the effect of intramolecular interactions exceeds intermolecular interactions what strongly affect their properties in diluted and concentrated solutions.

In this paper, we report 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) supported high-pressure approach enforcing Ring-Opening Polymerization (ROP) of γ-butyrolactone (GBL), that due to unfavorable thermodynamics and low ring strain, is considered as a hardly polymerizable monomer. Application of Broadband Dielectric Spectroscopy (BDS) allowed us to find optimal thermodynamic conditions to perform well-controlled and notably fast polymerization (even within 1 h!), avoiding undesired crystallization process. It was shown that by varying pressure and temperature conditions, we could control molecular weight, dispersity of recovered macromolecules, as well as rate and efficiency of the reaction that are significantly altered with respect to the reference process carried out at ambient conditions. Experiments performed at respectively very low temperature T = 233 K and low/moderate pressure (p = 75–250 MPa) and much higher temperatures (T = 248–268 K) and compressions (p = 1000 MPa) yielded poly(γ-butyrolactone) (PGBL) of tailored absolute molecular weight in moderate range Mn = 2.8–15.0 (up to 30.3) kg/mol and narrow/moderate dispersity ranging from Đ = 1.12–1.89. What is more, the implementation of MALDI-TOF, GPC and DSC analyses, clearly indicated that as i) the time of reaction gets longer, ii) the amount of catalyst increases, iii) the temperature lowers, the content of cyclic products in produced polymers grows. This phenomenon influences the rheological properties (viscosity), foil formation ability (films) and cell culture proliferation features of the recovered macromolecules. Presented results open a highly effective and repeatable route to produce PGBL via pressure-assisted ROP and indicate the possibility of tuning properties of this polymer by varying concentration of cycles or eventual block copolymerization with other biorelevant monomers to meet the expectations of the biotechnological industry.

Microbial infections lead to elevated inflammatory responses, which usually result in prolonged and incomplete wound healing. Therefore, there is an increasing demand for biodegradable fibres that are effective against a different range of microorganisms, especially those with antibiotic resistance. Herein, quercetin-(Q)-loaded polylactide-based fibres were developed using the electrospinning technique. Since Q exhibits low chemical stability, we used star-shaped polylactides (PLAs) with a β-CD core to host Q by inclusion complexation. To enhance the stability of the fibres and additionally entrap the Q between polymeric chains, we adapted supramolecular cross-linking by the stereocomplexation of PLAs with opposite configurations. As a control, we prepared an additional formulation of star-shaped/commercial PLA/Q for the preparation of nonwovens in which the β-CD moiety was not present. All developed fibres were smooth and continuous, with an average diameter of 37 μm. Although nonwovens did not possess diffusible activity, good antibacterial effects against Staphylococcus aureus (S. aureus), Escherichia coli (E.coli) and Klebsiella pneumoniae (K. pneumoniae) were observed. All these features validate the proposed approach, in which different supramolecular interactions were used to modify the properties of PLA-based fibres and, most importantly, show their great potential usefulness against microbial infections.

The designing of biocompatible nanocarriers for the efficient delivery of their cargos to the desired targets remains a challenge. In this regard, the most promising strategy relies on the construction of pH- or thermo-responsive nanoparticles (NPs). However, it is also important to preserve the balance between the responsiveness of the carrier and their stability in physiological conditions. Therefore, we described a new family of copolymers of lactide and allyl-glycidyl ether which were subsequently modified by thiol-ene reaction to functionalize the resulting copolymer with acetylcysteine (ACC) or thioglycolic acid (tGA) moieties. Subsequently, these copolymers were used to obtain blank and doxorubicin (DOX) loaded NPs with an average diameter of about 50−100 nm. Interestingly, the NPs were stable in different pH conditions, however, the presence of ACC or tGA units in the polymeric chain allows for the reduction of the undesired burst release due to the supramolecular interactions between polymeric pedant groups and DOX. The release tests of DOX from NPs showed that DOX release rate decrease depending on the pH values and the copolymer functionalization in order of non-modified NPs > ACC-modified NPs > tGA functionalized NPs. Most importantly, the MTT assay showed that all blank NPs are non-toxic against the normal L929 cell line. Subsequently, the antitumor efficiency of the obtained NPs was tested towards L929 (murine fibroblast cell line), HeLa (cervical cancer), and AGS (human gastric adenocarcinoma cancer) cells. The results demonstrated that DOX-loaded NPs efficiently induce the reduction in the viability of the HeLa and AGS cell, and this reduction in the viability was even below 20 % for the AGS cells. Together with their biocompatibility, the obtained NPs offer a novel route for the preparation of nanocarriers for the controlled and efficient delivery of anticancer drugs.

In this study, the influence of homehold composting conditions on the molecular and supramolecular structure of polylactide (PLA) in the form of spun-bonded nonwovens was investigated. Nonwoven samples were studied using size-exclusion chromatography coupled with multiangle laser light scattering detection, wide-angle X-ray diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy. In addition, the physical and mechanical properties of the nonwovens before and after composting were determined. The results show the varying degree of influence of the prepared compost mixtures of soil with common horticultural additives, such as chalk, commercially available agents, cow manure and chicken litter, on the molecular and supramolecular structure of PLA and its degradation rate. The obtained experiment explained which popular homehold agent had the strongest affect on the PLA nonwoven dedicated for agriculture use in the first period of season composting (first 6 months).

Medium molecular weight polylactides (PLAs) with different end groups were synthesized and analyzed by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Four types of end groups were introduced as head group using appropriate initiators: cationic group [ionic liquid group (IL-PLA-OH)], easily ionizable groups [aminopyridine group (AmPy-PLA-OH) and terpyridine group (TerPy-PLA-OH)], and neutral group [butoxy group (Bu-PLA-OH)]. MALDI-TOF spectra were recorded with various cationizing agents (Li+, Na+, and K+ salts). Different modes of ionization were observed depending on the nature of end group. These various modes of ionization lead to different ionization efficiencies, which affect signal intensity. Moreover, analysis of 1/1 mixtures showed that in spectra of mixtures of IL-PLA-OH with either AmPy-PLA-OH or Bu-PLA-OH, only the signals of IL-PLA-OH were detected, while in the spectrum of AmPy-PLA-OH with Bu-PLA-OH, the former gave signals with intensity about one order of magnitude higher than the latter. Such discrimination resulting from different modes and efficiencies of ionization of macromolecules containing structurally different end groups may lead to erroneous conclusions.

This paper presents an overview of our recent work concerning supramolecular polylactides. It is based on the lecture given at 58th Annual Scientific Meeting of the Polish Chemical Society in September 2015. New synthetic methods and the phenomena related to the formation of supramolecular aggregates of enantiomeric polylactides and their stereocomplexes are presented. A combination of two kinds of supramolecular interactions: the ones between enantiomeric polylactide chains with opposite configuration and those between the complementary end groups of polylactide macromolecules, leads to the formation of materials with different morphology and thermal properties. The main methods used to investigate the process of self-assembly of enantiomeric polylactides and their stereocomplexes are also presented.

Linear and star-shaped polymers have been synthesized by the controlled ring-opening (ROP) polymerization of l - and d -lactide using 1-methyl-2-hydroxymethyl-3-butylimidazolium tetrafluoroborate and dipentaerythritol as initiators, respectively. To introduce carboxylic end-groups onto the star-shaped polylactides, the reaction of –OH end-groups with succinic anhydride was employed. Afterwards, the starting and modified polylactides were used for the preparation of star-shaped and star-shaped/linear stereocomplexes in 1,4-dioxane and tetrahydrofuran (THF). In these solvents, the stereocomplexes spontaneously precipitated. Star-shaped stereocomplexes with hydroxyl end-groups formed microspheres with diameters ranging from 1 to 4 μm (depending on the initial concentration of sc-PLA components) following precipitation from THF. However, the combined effect of the nature of the end-groups and PLA architecture causes the formation of uniform stereocomplex nanoparticles (∼400 nm) in 1,4-dioxane from the combination of star-shaped PLA functionalized with carboxylic end-groups and linear PLA with ionic liquid end-groups. Microscopic analysis showed that nanometre-sized grains of stereocomplexes (∼30 nm) aggregated to form larger stereocomplex nanoparticles. It was observed that the combination of three factors, i.e., the end-group interactions, architecture of the enantiomeric components, and basicity of the solvent in which the stereocomplexes are prepared, influences the properties and morphology of the final stereocomplex-based materials.

The delivery of atropine (AT) in the conventional form often exerts systematic side effects, including fever, convulsion or even death. Therefore, the novel microparticles drug delivery systems could be ideal to minimize the dose and toxicity of AT. For this purpose, we propose the use of stereocomplexed spherical microspheres with a diameter of 2 μm loaded with AT to be administered through the ocular route. The spontaneous precipitation was employed to prepare microspheres from poly- l -lactide (PLLA) and poly- d -lactide (PDLA) with methyl-β-cyclodextrin (MnβCD) or dipentaerythritol (DPE) core which can host the hydrophobic drugs in its interior. We could demonstrate that for a model system composed of MnβCD the inclusion of AT in CD cavity can be achieved. Although the morphology and size of microspheres composed of PLAs with MnβCD and DPE do not differ significantly, the release of the AT was slower for the PLAs with MnβCD core. This means that by alteration of the microsphere building blocks: PLAs with MnβCD versus DPE core, we could modulate the drug release. Our findings not only provide a novel strategy to prepare Sc-PLA microcarriers with the controllable release of the cycloplegic agent but also offer the application of Sc-PLA microspheres in anti-myopia therapy, due to their suitable size for ocular administration.

Lung cancer is the leading cause of cancer death because of smoking and air pollution. Therefore, new ideas should be provided for lung cancer treatment in which the delivery of anticancer drugs to the local tumor site can be achieved. For this purpose, we propose the use of stereocomplexed spherical microspheres with sizes between 0.5 and 10 mu m loaded with doxorubicin (DOX) to be administered through the nasal route. In order to gain control over the microsphere morphology, size, and drug loading capacity, we systematically studied the influence of the solvent used for preparation and the functionalization of their building blocks, namely poly-L-lactide (PLLA) and poly-D-lactide (PDLA) with blocked or unblocked L-proline moieties. We could demonstrate that DOX release is generally determined by the size of the microspheres. The antiproliferative activity of DOX released from the different microspheres was shown in vitro using the A549 lung cancer cell line as a model. Moreover, when in direct contact to the cancer cells, smaller microspheres were uptaken and could serve as a reservoir for local drug release. Our findings not only provide a novel strategy to prepare PLA microspheres with controllable morphology and release of anti-cancer drugs but also offer additional possibilities for the application of stereocomplexed particles in anticancer therapy, with suitable sizes for nasal administration. M. Brzezinski and M. Socka acknowledges for support from the National Science Centre Poland Grant DEC-2016/23/D/ST5/02458. S. Wedepohl and M. Calderon gratefully acknowledge financial support from Bundesministerium fur Bildung and Forschung (BMBF) through the NanoMatFutur award (13N12561) and IKERBASQUE-Basque Foundation for Science.

The discovery of stereocomplexation, secondary interaction between enantiomeric poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) provides a method for the creation of novel biomaterials with distinctive chemical and physical stability. Stereocomplexation opens a new way for the preparation of diverse micro- and nanostructures such as uniform microspheres, hollow particles, micelles, nanocrystals, nanofibres, nanotubes and polymerosomes. Herein, we describe the design of stereocomplex assemblies for specific applications and methods for their preparation. This review focuses primarily on the use of stereocomplex assemblies in biomedical applications due to the improved stability and physicochemical properties in comparison to enantiomeric polylactides. To make the polylactide stereocomplexes soluble in water and, as a consequence, to improve compatibility with the human body, various amphiphilic copolymers with PLLA and PDLA enantiomeric segments can be prepared. Stereocomplexation can facilitate their self-assembly into micro- and nanoparticles, stabilize the particle size and morphology and can also have an influence on the in vivo degradation rate and cytotoxicity of these materials. Stimuli-responsiveness in stereocomplex assemblies can be achieved by copolymerization of lactide with, for example, thermoresponsive N-isopropylacrylamide or amino acids with pH-sensitive pendant groups. Stereocomplex micro- and nanoparticles are used for encapsulation of various bioactive compounds: anticancer drugs, antibiotics and proteins. Finally, examples of materials in which high thermal and mechanical stabilities delivered as a result of stereocomplexation play a crucial role, i.e. hydrogels, nanofibres, microcellular foams and artificial skin, are described. The preparation of biomaterials and biomedical systems based on polylactide stereocomplex assemblies opens new opportunities in this field. © 2015 Society of Chemical Industry

The controlled ring-opening polymerization of l-lactide and d-lactide using 2-aminopyridine (AP), isocytosine (IC), uridine (U), and 2-ureido-4[1H]-pyrimidinone (UPy-OH) initiators with stannous(II) octanoate as catalyst leads to polylactides (AP-PLA-OH, IC-PLA-OH, U-PLA-OH, and UPy-PLA-OH), which are capable of forming strong hydrogen bonds and consequently self-assemble. By means of “1H NMR titration”, the association constant (Ka) was determined for chosen model system composed of polylactides with uridine and aminopyridine end groups. The coupling reaction of UPy-PLA-OH with diisocyanates was used to obtain PLLA and PDLA with UPy end groups on both sides of the chain: UPy-PLLA-UPy and UPy-PDLA-UPy. The SEC analysis of the telechelic UPy-PLA-UPy revealed the presence of a supramolecular polymer with a high-molecular-weight fraction (Mn ≈ 70 000 g/mol) compared with the molar mass of the starting dimer (UPy-PLA-OH, Mn ≈ 7000 g/mol), which confirms the strong complementary interactions of the end groups....

In this paper, the influence of the various degradation conditions, on the molecular and supramolecular structure of polybutylene succinate (PBS) and polybutylene succinate adipate (PBSA) copolymer during degradation time is described. Experiment was carried out by the use injection molded samples and normalized conditions of biodegradation in soil, composting and artificial weathering. Materials were studied by using size-exclusion chromatography (SEC) coupled with multiangle laser light scattering (MALLS) detection and wide-angle X-ray diffraction (WAXD). Additionally, the physical and mechanical properties of the samples were determined. The performed experiments clearly show difference impact of selected degradation condition on the macroscopic, supramolecular and molecular parameters of studied aliphatic polyesters. The structural changes in PBS and PBSA explain the observed changes in the physical and mechanical properties of the obtained injection molded samples.

A series of well-defined amphiphilic graft copolymers based on poly(propylene glycol)methacrylate (PPGMA) extended with a polymethacrylate segment containing methacrylic acid units was successfully synthesized, combining atom transfer radical polymerization (ATRP), esterification, “grafting from” polymerization, and acidolysis. The multistep procedure yielded hydroxy-functionalized polymers (6–47 mol% of PPGMA), bromoester-functionalized copolymers as multifunctional macroinitiators (nBr = 8–25), PPGMA-based copolymers with poly(tert-butyl methacrylate) (PtBMA) segments (DPtBMA = 18–59), and copolymers varying in hydrophilic fraction content (FMAA = 0.28–0.54). After the generation of methacrylic acid units the PPGMA-based graft polymers attained a good solubility in polar solvents such as methanol and water. The particles, which were formed in aqueous solution, achieved sizes in the nanoscale range (165–230 nm) and negative zeta potentials.

Biomimetic composites based on star-shaped poly(2,2-dimethyl trimethylene carbonate)s fitted with carboxyl end-groups (PDTC(COOH)4) and hydroxyapatite (HA) were prepared using grinding technique under solvent free conditions. The required carboxyl groups were introduced at the polymer by reaction of hydroxyl groups with succinic anhydride. The synthesis of star-shaped, hydroxyl terminated precursors was achieved applying ring-opening polymerization of 2,2-dimethyl trimethylene carbonate (DTC) conducted in the presence of multi-hydroxyl alcohol as an initiator and tin octoate (Sn(Oct)2) as a catalyst. The thermal properties of obtained polymers were studied by DSC and TGA. Composites containing 15 wt% of HA were characterized regarding the HA distribution in the polymer matrix, crystallinity and thermal stability. Mechanical studies have demonstrated that PDTC(COOH)4/HA composites exhibit very good mechanical properties characterized by the elastic modulus (264 MPa and 365 MPa) in the range of the elastic modulus of cancellous bone.

The synthesis of monomodal copolymers with poly(ethylene glycol) (PEG) side chains from commercial poly(ethylene glycol) methacrylates (PEGMA) by atom transfer radical polymerization (ATRP) is verified. Two hydroxy-functionalized PEGMA macromonomers (520 g/mol and 360 g/mol) were copolymerized with methyl methacrylate (MMA) using various initial feed (1.5/98.5–50/50 mol.%). The copolymers P(MMA-co-PEGMA) with high degree of polymerization, e.g. 100–275 of repeating units in the backbone including 7–56 PEG side chains, were obtained. The relative reactivity ratios of PEGMA and MMA determined by the Jaacks method indicated slightly faster incorporation of macromonomer into polymeric chain than MMA (rMMA = 0.79; rPEGMA = 1.27). The polymers containing at least 17 mol.% of PEGMA units were water-soluble and exhibited clouding point at temperature in a broad range of 39–70 °C. The temperature-sensitive effect makes these polymers as a potential carriers in drug delivery systems. In the case of copolymers insoluble in water, a three-step procedure, including esterification to ATRP multifunctional macroinitiators, ATRP of tert-butyl methacrylate (tBMA) by grafting from, deprotection of carboxylic groups by removing tert-butyl groups, was applied to extend PEG grafts and expand the content of hydrophilic fraction (32–94 mol.%), what efficiently developed polymer solubility in polar solvents giving possibility for the future biomedical applications.

Poly(lactide)-carbon nanotubes nanocomposites (PLA–CNTs) with poly(lactide) (PLA) covalently attached to CNTs show enhanced mechanical and thermal properties. Two methods of CNTs modification were mainly employed: “grafting from” and “grafting to”, to improve their key parameters affecting the properties of composites – the dispersion and compatibility with PLA matrix. On the other hand stereocomplexation of enantiomers of PLA also leads to acquire the PLA-based materials with improved thermal-resistance, mechanical properties and the hydrolysis-resistance. PLA–CNTs stereocomplex nanocomposites are novel materials with unique properties due to synergic effect of carbon nanotubes and stereocomplexation. This featured letter reports recent developments in this new field.

Biocompatible and biodegradable stereocomplexed micelles (SCMs) based on polylactides (PLAs) with β-cyclodextrin (β-CD) core were designed and used as efficient intracellular drug carriers. The micelles formation, stability and drug release behavior of enantiomeric and stereocomplexed micelles with β-CD core were systematically investigated in comparison to the micelles composed of PLAs with dipentaerythritol (DPE) core. The presence of β-CD core allows for the formation of inclusion complex with a model anticancer drug: doxorubicin (DOX), whereas stereocomplexation between PLLA and PDLA enhanced the stability of obtained micelles. By the utility of different supramolecular interactions, we were able to control the release of DOX from obtained micelles. The release tests of DOX from supramolecular nanocarriers showed that DOX release changes in the order of DPE core micelles >β-CD core micelles >SCMs. The antitumor activities of the enantiomeric and stereocomplexed micelles toward HeLa (cervical cancer) and K562 (chronic myelogenous leukemia) cells were tested in vitro. Our data demonstrated that the SCMs/DOX more effectively inhibited the cell proliferation than similar enantiomeric micelles and for the highest concentration of DOX inside the SCMs. Most importantly, micelles were more efficient than free DOX. In summary, the supramolecular interactions can provide a favourable tool to construct a drug delivery system with controlled drug release and efficient tumor cell suppression which is beneficial for cancer therapy.

In this paper, the combined effect of the infl uence of polylactide (PLA) end-group nature and PLA architecture on the morphology of stereocomplexes formed during precipitation from organic solvent is investigated. Stereocomplexation of star-shaped poly( L -lactide) and linear poly( D -lactide) functionalized with imidazolium ionic liquid end groups in 1,4-dioxane leads to the formation of uniform microspheres, which are able to crystallize in the form of colloidal crystals. Microscopic scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis show the hierarchical structure of the system starting from the nanometrical grains composed of few stereocomplex macromolecules that aggregate in uniform microspheres fi nally forming colloidal crystals of microspheres.

Well-defined amphiphilic graft copolymers containing hydrophilic poly((meth)acrylic acid) (PMAA) or poly(acrylic acid) (PAA) side chains with gradient and statistical distributions were synthesized. For this purpose, the hydroxy-functionalized copolymers with various gradient degrees, in which 2-(6-hydroxyhexanoyloxy)ethyl (meth)acrylate units (caprolactone 2-[methacryloyloxy]ethyl ester, CLMA) formed strong gradient with tert-butyl acrylate (tBA), slight gradient copolymers with tert-butyl (meth)acrylate (tBMA), and statistical copolymers with methyl (meth)acrylate (MMA) were modified to bromoester multifunctional macroinitiators, P(tBMA-grad-BrCLMA), P(BrCLMA-grad-tBA), and P(BrCLMA-co-MMA). In the next step, they were applied in controlled radical polymerization of tBMA and tBA yielding graft copolymers with various lengths of side chains as well as graft densities. Further, the tert-butyl groups in copolymers were successfully removed via acidolysis in the presence of trifluoracetic acid, which caused transformation of the hydrophobic graft copolymers into amphiphilic ones with ability of self-assembly for the future biomedical applications. Copyright © 2013 John Wiley & Sons, Ltd.

The reactive oxirane groups were incorporated into the macromolecule as substituents in the side chains of loosely-grafted copolymer or in the arms of star-shaped copolymer using glycidyl methacrylate (GMA) in the controlled atom transfer radical polymerization (ATRP). The branched GMA copolymers with various architectures were obtained by using hydrophobic copolymers containing six and seven units of caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) functionalized with bromoester groups, and trifunctional poly(e-caprolactone) (PCL), as well as hydrophilic tri-, and six-functional acetal derivatives of D-glucopyranosides as (macro)initiators with biodegradable and biocompatible properties. The well-defined copolymers with core-shell structures and polymerization degrees of GMA in the range of 20–100 per side chain/arm at 20–70% of monomer conversion within 1–6 h and narrow molecular weight distributions (Mw/Mn = 1.14–1.4) were obtained. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers

A novel and simple method for the preparation of linear, high-molar-mass, thermally stable polylactide stereocomplexes (sc-PLA) with multiwalled carbon nanotubes (MWCNTs) covalently attached to enantiomeric PLA chains is presented. The MWCNTs modified with organic spacers terminated with −OH groups were used as initiators for the ring-opening polymerization (ROP) of enantiomeric l- and d-lactides. The weight percentage of MWCNTs in the final stereocomplexes was approximately 1 wt %. The nascent (as-polymerized) polymer samples obtained by the ROP in bulk at 130 °C exhibited unusually high melting temperatures (≥190 °C) as well as enthalpies of fusion close to that estimated for polylactides with 100% crystallinity. PLA stereocomplexes were prepared from equimolar mixtures of l-PLA and d-PLA that also contained MWCNT-g-PLA, either by precipitation from solution or, for the first time, as a thin film via the slow evaporation of solvent. Crystallization in the form of stereocomplexes after melting was, unusu...

Linear and star-shaped poly(e-caprolactone) (PCL) block copolymers containing poly(meth)acrylate segments with glycidyl, 2-(trimethylsilyloxy)ethyl and tert-butyl pendant groups were synthesized using mono-, di- and trifunctional PCL macroinitiators and appropriate (meth)acrylate monomers by controlled radical polymerization. The well-defined structures with narrow molecular weight distributions indicate the coexistence of semi-crystalline PCL and amorphous poly(meth)acrylic phases. The hydrophobic nature of the block copolymers can be easily converted to amphiphilic, which with biodegradable and biocompatible PCL segments are promising as polymeric carriers in drug delivery systems. © 2012 Society of Chemical Industry

A series of new well-defined copolymers containing the hydroxyl-functionalized monomer, caprolactone 2-(methacryloyloxy)ethyl ester (CLMA), and tert-butyl acrylate/methacrylate (tBuA/tBuMA) were synthesized via atom transfer radical polymerization (ATRP). The composition of copolymer strongly depended on the selection of comonomer pair. The relative reactivity ratios of comonomers determined by the Jaacks method indicated significantly higher reactivity of CLMA in methacrylate/acrylate system (rCLMA = 2.53, rtBuA = 0.40), whereas tert-butyl monomer was faster polymerized in case of two methacrylates (rCLMA = 0.61, rtBuMA = 1.63). These results were compared with that obtained for the CLMA/MMA system, which was closer to CLMA/tBuMA, giving rCLMA = 0.83 and rMMA = 1.20. The copolymer composition influenced the glass-transition temperatures (Tgs), which decreased with an increase of CLMA content.

A series of P(MMA- co -CLMA) copolymers with different ratios of both components were prepared by copolymerization of 6-hydroxyhexanoic acid 2-(2-methacryloyloxy)ethyl ester commercially known as caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) with methyl methacrylate (MMA) via atom transfer radical polymerization (ATRP) using various catalytic and initiating systems. The narrow molecular weight distribution of the resulted functional copolymer containing small amounts of hydroxyl groups was broadened with the content of CLMA. Further, the P(MMA- co -CLMA) after modification was used as the multifunctional macroinitiator for “grafting from” polymerization of MMA. The composition of copolymers was confirmed by proton nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FT-IR). Thermal analysis by differential scanning calorimetry (DSC) indicated that the addition of CLMA units into PMMA backbone lowered glass transition temperature ( T g ), whereas later it was increased by the grafting of PMMA side chains.

We report systematic structural studies of poly(l-lactide) (PLLA) employing matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and solid-state NMR spectroscopy. (13)C cross polarization magic angle spinning (CP/MAS) NMR data for 1,8-dihydroxy-9-anthracenone (DT), 2,5-dihydroxybenzoic acid (DHB), 2-(4-hydroxyphenylazo)-benzoic acid (HABA), and trans-3-indoleacrylic acid (IAA), four matrices commonly used in MALDI-TOF analysis of polymers, were analyzed to test the influence of crystallization conditions (solvent, inorganic salt) on sample morphology. (13)C principal elements of chemical shift tensor (CST) and line-shape analyses were employed to study of the nature of hydrogen bonding and to evaluate the crystallinity and amorphicity of the pure polymer. NMR parameters for PLLA were compared with data for polylactide crystallized with the four matrices under different conditions with the addition of two inorganic salts as cationization agents. This study revealed that the semicrystalline structure of the polymer does not change when it is embedded in the matrix.

Summary — Stereocomplexes composed of 6, ~13, 24 and 32 arm star-shaped poly(lactide)s (ss-sc-PLAs) and of the mixed star-shaped — linear PLAs (sl-sc-PLAs) were prepared in a controlled way. Their thermal properties were characterized by DSC and compared to their linear counterparts properties. It was observed that the equimolar mixtures of star-shaped (R)-PLA and (S)-PLA crystallize during precipitation into methanol from the methylene chloride solution preferentially in the form of the highly crystalline (up to 70 %) stereocomplexes. The star-shaped PLA stereocomplexes with the number of arms higher than six (i.e. ~13, 24 and 32) survived melting and after slow cooling during the second heating run crystallized once again showing exclusive stereocomplex formation. After melting and annealing at high temperature and then fast cooling to the room temperature, in the second heating run also only two peaks in thermograms appeared exothermic cold crystallization peak (Tccsc) and endothermic melting peak (Tmsc) for star-shaped sc-PLAs with ~13, 24 and 32 arms. For high molar mass linear, mixed star-shaped — linear and six arm star-shaped stereocomplexes additional (R)-PLA and (S)-PLA homo-crystallites melting peaks appeared. These results show that thermal stability of stereocomplexes is strongly influenced by the topology and the number of arms in the star-shaped components.

Recent advances in the controlled ring-opening polymerization of aliphatic cyclic esters are briefly reviewed. Particular attention is paid to the high molecular weight linear, branched, and star-shaped poly(lactide)s and poly(e-caprolactone) synthesis. It is concluded that despite the plethora of initiating and/or catalytic systems applied for this purpose the best results so far were achieved with Al- and Sn(II) derivatives. Analytical methods employed for aliphatic polyesters of various architectures characterization, including SEC-MALLS, LC-CC, and fluorescence spectroscopy, are also discussed.

Star-shaped polymers, bearing a strictly defined number of linear arms, provide useful model structures for studies of branched macromolecular structures. In the dynamically growing area of biocompatible and biodegradable polymers, the synthesis and characterization of starshaped aliphatic polyesters are particularly advanced. Among others, some of our recent articles report the synthesis and characterization of 1-, 2-, 3-, 4-, 5-, 6-, 8, 13-, and 32-arm star-shaped poly(L-lactide)s by size exclusion chromatography (SEC), liquid chromatography under critical conditions (LC–CC), two-dimensional LC–CC/SEC, NMR, and fluorescence spectroscopy. The method perhaps most commonly used for starshaped polymer synthesis is based on the core-first approach, in which a multifunctional reagent (the core) plays the role of the (co)initiator and/or transfer agent. Another possibility in this area, originally developed by Rempp et al. for a styrene/divinylbenzene (DVB) system, was followed more recently by Lapienis and Penczek for an epoxide/diepoxide system. The principle of this approach is based on a two-step synthesis with the one-pot, arms-first coremethod. In the first step, a linear living polymer (the precursor) is prepared (e.g., polystyrene or polyepoxide). Then, in the second step, the resulting precursor initiates the polymerization of a tetrafunctional monomer (e.g., DVB or diepoxide), giving a highly branched macromolecular structure (the core). This communication reports the successful synthesis of highly branched, star-shaped aliphatic polyesters from various lactone and lactide/bislactone systems—e-caprolactone (CL)/5,50-bis(oxepan-2-one) (bis-CL), L,L-lactide (LA)/ bis-CL, CL/1,6-dioxaspiro[4,4]nonane-2,7-dione) (bis-BL), and LA/bis-BL—with aluminum isopropoxide [Al(OPr)3] as the initiator. Experimental evidence of the formation of starlike structures is provided by SEC and matrixassisted laser desorption/ionization time-of-flight (MALDITOF) analysis.

Following our previous papers on the mechanism of e-caprolactone (CL) and l,l-lactide (LA) polymerization initiated by tin(II) octoate [(tin(II) bis(2-ethylhexanoate), (Sn(Oct)2)] in the presence of the hydroxyl-group-containing compounds [H2O, alcohols or hydroxy-carboxylic acids (ROH)] the present work shows that the CL or LA/Sn(Oct)2/primary amine (RNH2) system, in principle, does not differ mechanistically from the CL or LA/Sn(Oct)2/ROH system. 1H NMR, matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometric and kinetic studies reveal that, in the first step of polymerization initiated with the Sn(Oct)2/RNH2 mixtures, formation of the α-amido-ω-alcohol (RNH-m-H (R‘OH)) (in which m denotes the repeating unit derived from CL or LA) proceeds. Then, the further steps of polymerization follow with R‘OH as co-initiator. Thus, eventually, the Sn(Oct)2/RNH2-initiated polymerization proceeds by the monomer insertion into the ...-Sn−OR‘ ‘ bond, reversibly formed in the react...

A review reports on application of amines as (co)initiators in the ring-opening polymerization of aliphatic cyclic esters. First, the use of tertiary amines (R 3 N) as initiators of the controlled polymerization of highly strained, four-membered β-lactone (P-propiolactone, PL) is described [equation (1)]. Then attempts at the high temperature polymerizations of the medium strained, six- and seven-membered δ- and e-lactones initiated with primary amines (RNH 2 ) or α-amino acids are briefly discussed. Finally, it is shown in more detail that the best results have been obtained recently in the processes catalyzed additionally with tin(II) octoate [Sn(Oct) 2 ]. Mechanisms of these polymerizations are also discussed. Results of the kinetic studies [equation (9) and (10)] as well as 1 H NMR, MALDI TOF mass spectrometry, and size exclusion chromatography (SEC) measurements, carried out in the authors' laboratory, indicate that polymerizations of £-caprolactone (CL) or L,L-lactide (LA) initiated with RNH 2 /Sn(Oct) 2 fulfill living process criteria and therefore allow to fully control the syntheses of the corresponding polymers. The selected syntheses applications, such as preparation of the copolymers N-carboxyan-hydrides of α-aminoacids and LA [equation (7)] or star-shaped polymers based on polyamino dendrimers [formula (I) and (II)] are also described.

Star-shaped poly(lactide)s (PLAs) with various numbers of secondary OH-groups at the PLA's arm ends and primary OH-groups attached directly to the core of the star were analyzed under critical conditions determined for linear PLAs. The same set of PLAs was then analyzed after blocking the core OH-groups with benzyl moieties. Depending on the number and the placement of the OH-groups in the star polymer different elution behavior was observed. As expected, on a ‘normal’ phase column, increasing the number of functional OH-groups results in a stronger interaction with the stationary phase and therefore in a larger retention volume. Keeping the number of functional groups constant, but varying the number of arms leads to a minimum in retention volume for the four arm star-shaped PLAs. The elution behavior could be discussed quantitatively on the basis of theories for polymer chromatography for large and small pores. It was possible to derive the parameters necessary to quantitatively fit the experimental results. The model for large pores and the model for small pores result in equally good descriptions of the experimental data.

Linear telechelic, α,ω-ditelechelic, and star-shaped tri-, tetra-, penta-, and hexa-arm poly(L-lactide)s (PLAs) fitted at every arm with pyrene end group have been prepared. Internal dynamics and mobility of the PLA chains in tetrahydrofuran solution at 25 °C, with regard to the number of PLA arms in one macromolecule and the individual arm average degree of polymerization, was followed by fluorescence spectroscopy. Analysis of both static and time-resolved spectra of the star-shaped polymers revealed dynamic segmental motion resulting in end-to-end cyclization, accompanied by an excimer formation. Probability and rate of the latter reaction increased with increasing number of arms and with decreasing their polymerization degree. Moreover, time-resolved measurements revealed that for macromolecules containing few arms (2 or 3) the pyrene moieties are located in the interior of the star-shaped PLAs, whereas in the instance of the higher number of arms (4–6) they are located at the periphery of the star-shaped PLAs. Thus, increasing the number of arms leads to their stretching away from the center of the star-shaped PLA macromolecule. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4586–4599, 2005

Star-shaped poly(L-lactide)s (PLAs) bearing variable numbers of secondary hydroxyl groups at linear arms chain-ends and primary hydroxyl groups directly attached to dipentaerithritol core (DPE) ((HO)6−xDPE(PLA-OH)x, where x = 1–6) were prepared and then analyzed by means of size exclusion chromatography (SEC), 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and eventually by Liquid Chromatography at Critical Conditions (LC-CC). First, starting from DPE(OH)6 a series of polyols with various number of hydroxyl groups has been obtained ((BnO)6−xDPE(OH)x, where Bn denotes benzyl moiety and x = 1–6). The living ring-opening polymerization of L-lactide (LA) with (BnO)6−xDPE(OH)x/tin(II) octoate mixtures as initiating and catalytic system led to star-shaped (BnO)6−xDPE(PLA-OH)x polymers with molar masses (Mn) controlled by LA and DPE concentrations ratio in the feed. Finally, deprotection (via hydrogenation) gave a series of (HO)6−xDPE(PLA-OH)x PLA's. SEC (with Multiangle Laser Light Scattering Detector (MALLS)), NMR, and MALDI-TOF analyses confirmed the assumed structures and Mn's of the prepared (BnO)6−xDPE(PLA-OH)x and (HO)6−xDPE(PLA-OH)x PLA's. LC-CC measurements revealed that for (BnO)6−xDPE (PLA-OH)x series the elution volumes increase monotonically with the increasing number of –PLA-OH arms in one macromolecule and are independent on the given PLA molar mass because of the critical conditions. Contrary to the polymers having the protected core hydroxyl groups, the elution volume for (HO)6−xDPE(PLA-OH)x series decreases with the increasing number of -PLA-OH arms reaching a minimum value for 4-arm PLA and then slightly increases for 5- and 6-arm PLA. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6116–6133, 2005

α-Ester-ω-hydroxy terminated poly(L-lactide) [C 4 H 9 OC(O)--PLA-OH] was prepared by the ring-opening polymerization of L,L-dilactide using tin(II) 2-ethylhexanoate [tin octoate, Sn(Oct) 2 ]/BuOH system or tin(II) butoxide as initiators in a wide range of molecular weights (M n ): from 10 3 up to 7 10 5 . Thermal degradation behavior of C 4 H 9 OC(O)-PLA-OH was then compared with that of its esterified counterpart [C 4 H 9 OC(O)-PLA--OC(O)CH(C 2 H 5 )C 4 H 9 ]. Thermogravimetric measurements versus M n revealed, as a result of M n →∞ extrapolation, the upper limit of thermal resistance of poly(L-lactide) (PLA). The onset temperature of the thermal degradation (OT) and the temperature of maximum degradation rate (MDT) of PLA are equal to 337 and 376 °C, respectively. Despite the deteriorating effect on the PLA molecular weight caused by in situ esterification of the hydroxyl chain ends with Sn(Oct) 2 , largely unreacted in polymerization, certain improvement of PLA thermal stability due to this side reaction was also observed.