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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.

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.

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.

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.

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.

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

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.

A series of well-defined polymers with various content of reactive oxirane groups (25–100 mol%) were synthesized via atom transfer radical polymerization (ATRP). The acetal derivatives of methyl α-D-glucopyranoside used as bi-, tri-, and tetrafunctional initiators allowed us to design macromolecules containing a sugar moiety in the center with V- and star-shaped topologies, and a length of each polymethacrylate segment in the range of 30–75 units. Various degrees of oxirane ring opening via aminolysis with mono- and diamines (20–100 %) or azidation (100 %) have demonstrated that the reactivity of pendant epoxide groups incorporated into the polymer was strongly dependent on the nucleophile agent and reaction environment. The complete transformation in the reaction with ethylenediamine and sodium azide yielded amphiphilic copolymers with differential solubility (diamine-functionalized polymers in polar protic solvents, e.g., water, versus azide-functionalized polymers in polar aprotic solvents, e.g., dimethylformamide). A few polymeric forms, that is unimers (0.5–1 nm), micelles (5–30 nm), aggregates (170–290 nm) and superaggregates (> 4,500 nm), were indicated by DLS measurements of water-soluble ethylenediamine derivatives of copolymers. Both the epoxy-functionalized polymers and their modified derivatives are potential materials for biomedical applications.