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This work presents the results of research on the preparation of bioresorbable functional polyestercarbonates containing side carboxyl groups. These copolymers were synthesized in two ways: the classic two-step process involving the copolymerization of l-lactide and a cyclic carbonate containing a blocked side carboxylate group in the form of a benzyl ester (MTC-Bz) and its subsequent deprotection, and a new way involving the one-step copolymerization of l-lactide with this same carbonate, but containing an unprotected carboxyl group (MTC-COOH). Both reactions were carried out under identical conditions in the melt, using a specially selected zinc chelate complex, with Zn[(acac)(L)H2O] (where: L—N-(pyridin-4-ylmethylene) phenylalaninate ligand) as an initiator. The differences in the kinetics of both reactions and their courses were pictured. The reactivity of the MTC-COOH monomer without a blocking group in the studied co-polymerization was much higher, even slightly higher than l-lactide, which allowed the practically complete conversion of the comonomers in a much shorter time. The basic final properties of the obtained copolymers and the microstructures of their chains were determined. The single-step synthesis of biodegradable polyacids was much simpler. Contrary to the conventional method, this made it possible to obtain copolymers containing all carbonate units with carboxyl groups, without even traces of the heavy metals used in the deprotection of the carboxyl groups, the presence of which is known to be very difficult to completely remove from the copolymers obtained in the two-step process.

This work presents the results of research on the preparation of bioresorbable functional polyestercarbonates containing side carboxyl groups. These copolymers were synthesized in two ways: the classic two-step process involving the copolymerization of l-lactide and a cyclic carbonate containing a blocked side carboxylate group in the form of a benzyl ester (MTC-Bz) and its subsequent deprotection, and a new way involving the one-step copolymerization of l-lactide with this same carbonate, but containing an unprotected carboxyl group (MTC-COOH). Both reactions were carried out under identical conditions in the melt, using a specially selected zinc chelate complex, with Zn[(acac)(L)H

Vascular regeneration is a complex process, additionally limited by the low regeneration potential of blood vessels. Hence, current research is focused on the design of artificial materials that combine biocompatibility with a certain rate of biodegradability and mechanical robustness. In this paper, we have introduced a scaffold material made of poly(L-lactide-co-glycolide)/poly(isosorbide sebacate) (PLGA/PISEB) fibers fabricated in the course of an electrospinning process, and confirmed its biocompatibility towards human umbilical vein endothelial cells (HUVEC). The resulting material was characterized by a bimodal distribution of fiber diameters, with the median of 1.25 µm and 4.75 µm. Genotyping of HUVEC cells collected after 48 h of incubations on the surface of PLGA/PISEB scaffolds showed a potentially pro-angiogenic expression profile, as well as anti-inflammatory effects of this material. Over the course of a 12-week-long hydrolytic degradation process, PLGA/PISEB fibers were found to swell and disintegrate, resulting in the formation of highly developed structures resembling seaweeds. It is expected that the change in the scaffold structure should have a positive effect on blood vessel regeneration, by allowing cells to penetrate the scaffold and grow within a 3D structure of PLGA/PISEB, as well as stabilizing newly-formed endothelium during hydrolytic expansion.

Co-delivery of epothilone B (EpoB) and rapamycin (Rap) increases cytotoxicity against various kinds of cancers. However, the current challenge is to develop a drug delivery system (DDS) for the simultaneous delivery and release of these two drugs. Additionally, it is important to understand the release mechanism, as well as the factors that affect drug release, in order to tailor this process. The aim of this study was to analyze PLA–PEG micelles along with several types of microspheres obtained from PLA or a mixture of PLA and PLA–PEG as carriers of EpoB and Rap for their drug release properties and cytotoxicity against breast cancer cells. The study showed that the release process of EpoB and Rap from a PLA-based injectable delivery systems depends on the type of DDS, morphology, and polymeric composition (PLA to PLA–PEG ratio). These factors also affect the biological activity of the DDS, because the cytotoxic effect of the drugs against MDA-MB-231 cells depends on the release rate. The release process from all kinds of DDS was well-characterized by the Peppas–Sahlin model and was mainly controlled by Fickian diffusion. The conducted analysis allowed also for the selection of PLA 50/PLA–PEG 50 microspheres and PLA–PEG micelles as a promising co-delivery system of EpoB and Rap.

Various types of biodegradable polymers containing lactide, glycolide, caprolactone, and trimethylene carbonate units have been used to obtain ciprofloxacin (CFX)-enriched coatings developed on the Ti6Al7Nb alloy, intended for short-term therapy. In the first step, the surface of the Ti6Al7Nb alloy was modified, mostly according to sandblasting and anodic oxidation to obtain the TiO2 layer. Anodizing can be an effective method for preparing TiO2 coatings with osteoconductive properties. The polymer containing CFX molecules was deposited on the modified alloy, and Polymer + CFX/TiO 2 /Ti6Al7Nb systems were developed. CFX-enriched coatings adhered well to the surface of the previously modified alloy. Polymer layers maintain the topography of the alloy due to the development of the surface during the sandblasting method. As polymers intended for the study possess degradation ability, they are capable of releasing the incorporated drug. Antibacterial activity of CFX-enriched coatings was examined to verify the functionality of designed Polymer + CFX/TiO 2 /Ti6Al7Nb systems, and the bactericidal effect was confirmed for all cases. The presented study is an extension of previous, initial research and creates an overview of polyester or polyestercarbonate CFX-eluting coatings.

Nowadays, researchers in the field of agrochemicals are trying to find effective methods to limit the excessive usage of pesticides and protect the environment. One of the most popular and promising techniques is the immobilization of pesticides using environment-friendly polymers. In the conducted research, it was demonstrated that the family of lactide/glycolide copolymers are unsuitable for this purpose due to very slow degradation in the soil. We examined influence of relatively small content of PEG blocks in newly synthesized poly( l -lactide-co-glycolide)-poly(ethylene glycol)–poly( l -lactide-co-glycolide) (PLGA–PEG–PLGA) on the degradation in soil, in activated sludge and usefulness of this terpolymers as a biodegraded carrier for the controlled release of two commonly used herbicides (Metazachlor and Pendimethalin). Presence of even small amount of PEG block in the terpolymer chain increases slightly the hydrophilicity of the polymeric chain, thereby increasing its susceptibility to hydrolytic and unexpectedly strongly to enzymatic degradation in soil environment. The amorphism of used as a carriers PLGA-PEG-PLGA terpolymers and the lack of the phenomenon of increasing the degree of crystallinity during degradation allow to achieve uniform progress of degradation, and thus is obtained a relatively constantly release of tested herbicides. In this way, it is possible to determine the optimal profile of degradation of polymer in soil and proper rate of diffusion and leaching of active agents which allows the release of herbicides in optimal and effective doses within 3–4 months of its application.

Glioblastoma multiforme is the most aggressive and lethal form of brain tumour due to the high degree of cancer cells infiltration into surrounding brain tissue. No form of monotherapy can guarantee satisfactory patient outcomes and is only of palliative importance. To find a potential option of glioblastoma treatment the bioresorbable, layer nonwoven mats for controlled temozolomide and nimorazole release were obtained by classical and coaxial electrospinning. Optimization of fibre structure that enables delayed and controlled drug release was performed. The studied bioresorbable polymers were poly(L-lactide-co-e-caprolactone) and poly(L-lactide-co-glycolide-co-trimethylene carbonate). The physicochemical properties of polymers were determined as well as drug release profiles of nonwoven mats. A combination of coaxial electrospinning and electrospray technique provided three-phased release profiles of temozolomide and nimorazole: the slow release of very low drug doses followed by accelerated release and saturation phase. Results form the basis for further investigation since both studied polymers possess a great potential as nimorazole and temozolomide delivery systems in the form of layered nonwoven implants.

Despite extensive development of bioresorbable drug-eluting vascular scaffolds it is still challenging to achieve controlled drug delivery. The lack of capacity for adjusting the drug dose and inadequate release behavior are one of the main reasons of the side effects. However, so far, mainly biodegradable drug-eluting coatings of metallic stents have been studied in regard to explain drug release mechanisms. The objective of this study was to develop degradable polymer coatings applicable to bioresorbable polymer-based scaffolds. Moreover, a detailed analysis of sirolimus release and scaffold degradation has been conducted. Coating layers of the same composition were applied by the same method on the surface of two different kinds of scaffolds in order to explain the effect of scaffold structure on release process. The developed coatings showed controlled release of antiproliferative agent with elimination of burst effect. However, differences in drug release profile from two kinds of scaffolds were observed. Scaffold composed of polymer with higher lactide content showed slower and bi-phasic, erosion-controlled release of sirolimus. On the contrary, sirolimus release from scaffold composed of polymer with lower content of lactide was mainly controlled by diffusion. These results demonstrate that characteristics of scaffold is another crucial factor that must be considered in further development of bioresorbable vascular scaffolds (BRS) with controlled release of antiproliferative agent.

Biodegradable coatings containing caprolactone units additionally enriched with ciprofloxacin formed on Ti6Al4V alloys have been developed. The polymer coatings were investigated as a carrier for ciprofloxacin-antibacterial drug. Coatings have been obtained according to the dip-coating method. Two kinds of polymers containing caprolactone units have been used: poly(glycolide-ɛ-caprolactone) and poly(glycolide-ɛ-caprolactone- d , l -lactide). The properties of the layered metal/polymer + drug system have been presented and the influence of the kind of polymer on the drug release has been evaluated. Different types of drug release profile depend on the type of used system. The CFX release from poly(glycolide-ɛ-caprolactone) is uniform with one stage, contrary to poly(glycolide-ɛ-caprolactone- d , l -lactide). The mechanism of ciprofloxacin release from GCap and GCapL matrices is different. The release from GCap and GCapL matrix fit to the Peppas-Sahlin and Korsmeyer-Peppas model, respectively. The release exponent indicates anomalous transport for GCap and case II transport for GCapL.

Localized drug delivery from vascular scaffolds can effectively prevent restenosis after stenting procedures. However, one of the current challenge remains to provide controlled release of antirestenotic drug and identify drug eluting mechanisms. The aim of study was to analyze the influence of polymer forming eluting layer, drug and intermolecular interactions on the release process. In vitro release of sirolimus or paclitaxel from coating of scaffolds obtained from poly( l , l -lactide)-co-trimethylene carbonate and poly( d , l -lactide)-co-trimethylene carbonate was studied. Differences between paclitaxel and sirolimus elution from crystalline copolymer were observed due to intermolecular interactions. Interaction of drug with amorphous polymer did not affect release process.

Sirolimus (rapamycin) is a antiproliferative drug used in vascular scaffolds for prevention of restenosis. Nowadays, the new generation of biodegradable drug-eluting vascular scaffold is extensively developed. However, the effective method for isolation of drug from a scaffold has not been developed yet. This procedure is important because it determines accuracy of quantitative assessment of drug, which is essential for evaluation of its dose or drug remained in the device after degradation. Therefore, the aim of the study was to develop the reliable method dedicated to bioresorbable scaffolds obtained from aliphatic polyesters and polyesterocarbonates for quantitative analysis of sirolimus. The results showed good precision of the extraction with the use of solvents and time-dependency of the sonication.

The control of the surface properties is an important issue for applicability of polymer membranes interacting with cells. In this work, the influence of surface roughness and stiffness of two polymer membranes on viability and mechanical properties of keratinocytes was studied. Terpolimer polyglicolide, polycaprolactone and polylactide, (PGA-PCL-PLA) and copolymer polycaprolactone, polyglicolide (PGA-PCL) substrates were used for membranes fabrication. Surface modification – the hydrolysis of the obtained membranes was carried out. The analysis of membranes’ surface properties revealed that RMS surface roughness and roughness factor of PGA-PCL-PLA membrane decreased after hydrolysis while its stiffness increased. In contrast, the PGA-PCL membrane stiffness was only slightly affected by NaOH treatment. Immortalized human keratinocytes (HaCaT) were grown under standard conditions on the surface of the studied membranes and characterized by means of atomic force microscopy and fluorescence microcopy. The results showed the substrate-dependent effect on cells’ properties.

The paper presents a synthesis of poly(l-lactide) with bacteriostatic properties. This polymer was obtained by ring-opening polymerization of the lactide initiated by selected low-toxic zinc complexes, Zn[(acac)(L)H2O], where L represents N-(pyridin-4-ylmethylene) tryptophan or N-(2-pyridin-4-ylethylidene) phenylalanine. These complexes were obtained by reaction of Zn[(acac)2 H2O] and Schiff bases, the products of the condensation of amino acids and 4-pyridinecarboxaldehyde. The composition, structure, and geometry of the synthesized complexes were determined by NMR and FTIR spectroscopy, elemental analysis, and molecular modeling. Both complexes showed the geometry of a distorted trigonal bipyramid. The antibacterial and antifungal activities of both complexes were found to be much stronger than those of the primary Schiff bases. The present study showed a higher efficiency of polymerization when initiated by the obtained zinc complexes than when initiated by the zinc(II) acetylacetonate complex. The synthesized polylactide showed antibacterial properties, especially the product obtained by polymerization initiated by a zinc(II) complex with a ligand based on l-phenylalanine. The polylactide showed a particularly strong antimicrobial effect against Pseudomonas aeruginosa, Staphylococcus aureus, and Aspergillus brasiliensis. At the same time, this polymer does not exhibit fibroblast cytotoxicity.

The local administration of different drugs in anticancer therapy continue to attract attention. Thus, the idea of local delivery of cytostatics from nonwoven-structured polyesters seems to be highly desirable. It could reduce systemic drug levels and provide high local concentration of the chemotherapeutics at the tumor site and contribute to enhance the efficiency of the anticancer therapy. Poly(glycolide-ɛ-caprolactone) (PGCL) and poly(D,L-lactide-co-glycolide) (PLGA) synthesized with zirconium-based initiator have been used to prepare electrospun, drug-eluting patches since they possess very good fiber-forming ability. Well-known chemotherapeutic drug-paclitaxel has been loaded into fibrous structure as a model anticancer agent in order to obtain drug delivery systems for local administration. The drug dose in obtained nonwovens might be regulated by the thickness and total area of the implanted patches. Electrospinning of PGCL/PLGA blend allowed to obtain soft and flexible implantable materials. Flexibility has been important factor since it ensures convenient use when covering a tumor or filling a resection cavity. The effectiveness of designed nonwovens presented in the study has been tested in vivo on mouse model of breast cancer. The growth of the tumors was slowed down during in vivo study in comparison with drug-free nonwovens- The volume of the tumor was 40% lower. Drug-loaded electrospun systems implanted locally to the tumor site was further combined with brachytherapy which improved the effectiveness of the therapy in about 18%. Detailed analysis of the nonwovens before and during degradation process has been performed by means of Scanning Electron Microscopy, Differential Scanning Calorimetry, Nuclear Magnetic Resonance, Gel Permeation Chromatography, X-ray Diffraction. The molar mass changes of the nonwoven were quite rapid contrary to changes of comonomer unit content, thermal properties and morphology of the fiber.

This study describes the preparation, physicochemical characterization and the biological studies of the polymeric delivery systems of proanthocyanidins (PCAN) extracted from Pelargonium sidoides for the potential use as wound dressings. In this study 20 wt% PCAN demonstrated good antimicrobial activity against Staphylococcus aures, a gram-positive wound pathogen. Poly(D,L-lactide) and atactic poly[(R,S)-3-hydroxybutyrate] biopolymers were used to construct biodegradable dressings. A series of polylactide/poly[(R,S)-3-hydroxybutyrate] (P(D,L)LA/a-PHB) blends, containing 10, 20, and 30 wt% of a-PHB were prepared and characterized by means of NMR, GPC, FT-IR, and DSC. Based on the findings, the P(D,L)LA/a-PHB [70/30 wt%] blend with the best thermomechanical properties (Tg value equal 37 °C) was chosen for the preparation of two kinds of electrospun mats, both with and without PCAN. About 50% of PCAN was released from the tested mats during the first 10–12 days of incubation. The electrospun mats with elastic properties, ensuring compatibility with the wound topology, were obtained. The studies of hydrolytic degradation of the constructed mats allowed us to gain complete knowledge of their hydrolysis process, and examine the PCAN release profile as well as identify and characterize the molecular structure of the degradation products of the developed delivery system. Furthermore, preliminary cytotoxicity MTT tests (in vitro) results support the potential application of PCAN-loaded (P(D,L)LA/a-PHB) electrospun mats in wound dressings.

A series of trimethylene carbonate/ l -lactide copolymers with varied comonomers composition were synthesized in bulk, using zinc (II) acetylacetonate and ethyl zinc (II) ethoxide as initiators. The values of the reactivity ratios were determined and they were respectively: r LA = 5.06 and r TMC = 0.89 in case of zinc (II) acetylacetonate and r LA = 13.3 and r TMC = 0.33 in case of ethyl zinc (II) ethoxide. Observed significant differences in reactivity of the comonomers and weak ratio of transesterification processes, resulted in formation of their specific, tapered chains microstructure. This phenomenon caused differences in physico-chemical properties compared to the previously presented TMC/ l -lactide copolymers obtained with other initiators. The presence of long lactidyl blocks caused much higher crystallinity of the copolymers. Investigation indicates on the spherolytic crystal morphology.

The paper presents the mechanism of lactide polymerization initiated with zinc (II) acetylacetonate monohydrate. However, the actual initiator of this reaction is the complex containing a metal–oxygen bond, formed by the exchange reaction of acetylacetonate ligand with deprotonated lactide derivative. The described reaction results in the release of free acetylacetonate and formation of transitional zinc complex with metal–oxygen bond connecting the zinc atom with derivative of lactide, incorporated – as a new, active in polymerization ligand. Polylactide chain propagation process, which constitutes the following stage of the reaction, is caused by a typical, well known, coordination-insertion ring opening polymerization. The proceeding polymerization maximum yield at the applied conditions does not exceed about 70% in benzene solution and 90% at bulk.

A hydroxylactone ((1R,5S)-1-hydroxy-3,6-dioxabicyclo [3.2.1] octan-2-one, abbreviated as LAC) obtained from catalytic pyrolysis of cellulose was investigated as a monomer in the synthesis of polyesters by ring-opening polymerization (ROP) with L-lactide. Although stannous octoate resulted inactive, ROP initiated by zirconium (IV) acetylacetonate afforded novel copolyesters from LAC and lactide mixtures in the bulk at 110 °C. Copolymers were obtained with different LAC content (from 19 to 45%) with a random microstructure as established by detailed NMR analysis. FTIR spectrometry confirmed the presence in the polymer chain of the OH groups originally present in LAC, which do not react during polymerization due to steric hindrance and inter/intramolecular hydrogen bonding. Reaction with trichloroacetylisocyanide proved that OH groups of the polyesters can be readily derivatized. The application of LAC as a comonomer enables the insertion of the alcohol functionality in polylactide avoiding protection/deprotection steps and potentially expanding the realm of biomaterials affordable from carbohydrate feedstock.

The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local treatment of periodontitis. Selected trimethylene carbonate/ϵ-caprolactone (TMC/CL) and glycolide/caprolactone (GL/CL) copolymers were synthesized and used as carriers in the form of small elastic rings with 5 wt% and 10 wt% doxycycline hyclate content, or in the form of flakes obtained through electro-spinning technique. The release of the drug under in vitro conditions has been tested. The study has shown that equimolar TMC/CL copolymer loaded with 10 wt% of doxycycline hyclate appears to be the most suitable copolymer for assumed system. The drug release proceeds mainly by diffusion of medium into the polymeric matrix and then the drug is washed out. Daily validation of doxycycline doses released by the system should ensure accurate course of the therapy.

Bioresorbable, aliphatic polyesters are known in medicine where serve as orthopedic devices (e.g., rods, pins and screws) or sutures and staples in wound closure. Moreover, such materials are extensively stud- ied as scaffolds--three-dimensional structures for tissue engineering but also drug delivery systems (DDS). The aim of this study was to determine the release profile of paclitaxel, one of the anti-inflammatory, antiprolifera- tive and anti-restenotic agent, from biocompatible copolymer of L-lactide and ε-caprolactone that seems to be very attractive especially for minimally invasive surgery due to its potential shape-memory property. The influ- ence of drug on copolymer hydrolytic degradation was also analyzed. Three types of matrices (3%, 5% of PTX and without drug) were prepared by solvent-casting method and degraded in vitro. The physicochemical changes of copolymer were analyzed by means of nuclear magnetic resonance spectroscopy (NMR), gel per- meation chromatography (GPC) and differential scanning calorimetry (DSC). The amount of drug released into media was monitored with the use of high-pressure liquid chromatography (HPLC). Similar drug release pro- files were obtained for matrices with paclitaxel. The drug-containing matrices degraded slightly slower than drug free matrices, regardless PTX content. Results of this work may be helpful in designing new bioresorbable paclitaxel delivery system applied in anti-cancer therapy or drug-eluting stents technology.

This article presents the results of TMC and DMC polymerization with the use of acetylacetonates of low-toxic metals: iron, zinc, and zirconium. Zinc (II) acetylacetonate proves to be a very good initiator of homopolymerization. The reaction carried out with the use of this initiator at 110 °C is very rapid and of high yield. Using both zinc and iron (III) acetylacetonates, as well as the zirconium (IV) one, in high temperatures it is possible to obtain PTMC possessing high molecular mass, thus ensuring optimization of the relation between the duration of the polymerization and its yield. A strong influence of thermal degradation on the course of the reaction has been observed, particularly at 160 °C, with the use of Fe(acac)3 as the initiator. DMC polymerization proceeds much more slowly when initiated by iron and zinc acetylacetonates. A high conversion of the monomer is obtained in this case as well. The relation between the molecular mass of the obtained PDMC and the conversion of the monomer is directly proportional; however, those masses, determined on the basis of polystyrene standards, are much lower than those estimated theoretically. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1913–1922, 2005

The possibility to obtain biodegradable high molecular weight aliphatic polycarbonates from trimethylene carbonate (TMC) and 2,2-dimethyltrimethylene carbonate (DTC) monomers with designed composition of comonomeric units was presented. Zinc(II) acetylacetonate monohydrate was used as a catalyst. A detailed analysis of copolymer chain structure was performed by means of high resolution 13C-NMR spectroscopy. The equations for calculation of characteristic parameters of copolymer chain such as average length of blocks, randomization and transesterification coefficients were shown. The copolymerization reactivity ratios were determined (rTMC = 1.17 ± 0.20 and rDTC= 0.42 ± 0.09). Significant differences in the reactivity of comonomers and the low transesterification result in gradient chain microstructure. The synthesized copolymer containing about 80 mol % of DTC units is a semicrystalline material with good mechanical properties, allowing for application of this material in the formation of bioresorbable flexible implants or scaffolds. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40037.

The aim of the following study was to evaluate the impact of premature rupture of membranes (PROM) on neonatal outcome, particularly on the incidence of intrauterine infections (IUI).The study included 428 newborns, born after PROM and hospitalized in the Department of Neonatology at Poznan University of Medical Sciences in 2006. The influence of selected variables on the development of IUI and other complications was analyzed.IUI occurred in 124 newborns (29%). The odds ratio (OR) of IUI incidence increased with decreasing gestational age, birth weight and Apgar score, as well as with increasing duration of the time between PROM and birth, called the latency period. Logistic regression showed that IUI was significantly influenced by the latency period (OR=1.37; 95% CI: 1.10-1.71; p0.01), gestational age (OR=2.29; 95% CI: 1.59-3.30; p0.0001) and 5-minute Apgar score (OR=2.50; 95% CI: 1.57-3,98; p0.001). The incidence of other complications such as prematurity respiratory distress syndrome, respiratory failure, intraventricular hemorrhage, and anemia increased with the duration of the latency period. Compared to uninfected infants, the infected ones were characterized by lower birth weight, lower gestational age, lower Apgar score and poorer laboratory results.Among neonates born from pregnancies complicated with PROM, the incidence of IUI is significantly influenced by the latency period, gestational age and 5-minute Apgar score. The incidence of other complications increases with the duration of the latency period. Prematurity is an important contributor to morbidity in this group of neonates.