Supramolecular Polypseudorotaxanes composed of star-shaped porphyrin-cored poly(epsilon-caprolactone) and alpha-cyclodextrin

Star-shaped porphyrin-cored poly(epsilon-caprolactone) (SPPCL) was synthesized using a tetrahydroxyethyl-terminated porphyrin as a core initiator and stannous octoate as a catalyst in bulk at 120 degrees C. The molecular weight of as-synthesized polymer could be adjusted linearly by controlling the molar ratio of epsilon-caprolactone to porphyrin core initiator, and the molecular weight distribution was reasonably narrow. Supramolecular polypseudorotaxanes were prepared by inclusion complexation of SPPCL with alpha-cyclodextrin (alpha-CD) and thoroughly characterized by means of FT-IR, 1H NMR, 13C CP/MAS NMR, DSC, TGA, and WAXD. The results demonstrated that the porphyrin-cored polypseudorotaxanes formed through alpha-CD molecules threading onto the branch chains of star-shaped SPPCL polymers, and they had a channel-type crystalline structure. Meanwhile, the original crystallization of SPPCL polymers within the polypseudorotaxanes was completely suppressed in the alpha-CD cavities. Moreover, inclusion complexation between SPPCL and alpha-CD enhanced the thermal stability of both the guest SPPCL polymers and the host alpha-CD. Furthermore, both the SPPCL polymers and the polypseudorotaxanes showed similar fluorescent and UV-vis spectra compared with porphyrin core initiator. Consequently, this will not only provide potentially porphyrin-cored poly(epsilon-caprolactone) and its polypseudorotaxanes for photodynamic therapy but also improve the compatibility between poly(epsilon-caprolactone) and peptide drugs for drug delivery.     

Novel amphiphilic poly(epsilon-caprolactone)-g-poly(L-lysine) degradable copolymers

As part of the search of novel degradable polymers, amphiphilic and cationic poly(epsilon-caprolactone)-g-poly(l-lysine) (PCL-g-PlL) copolymers have been synthesized following a grafting "onto" or a grafting "from" method both applied to a macropolycarbanionic PCL derivative. The first approach led to PCL-g-PZlL containing 36% of epsilon-caprolactone and 64% of N-epsilon-Z-l-lysine units, by reaction of activated poly(N-epsilon-Z-l-lysine) on the macropolycarbanion derived from PCL. The second route was based on the anionic ring opening polymerization of N-carboxyanhydride of N-epsilon-benzyloxycarbonyl-l-lysine initiated by the macropolycarbanion derived from PCL and led to a similar copolymer containing 45% of of epsilon-caprolactone and 55% of N-epsilon-Z-l-lysine units. After deprotection of the lysine units, PCL-g-PlL copolymers were obtained. These copolymers are water-soluble and form nanometric micelle-like objects with mean diameters between 60 and 500 nm in distilled water depending on the synthesis route.     

Synthesis and characterization of biodegradable hyperbranched poly(ester-amide)s based on natural material

A series of novel AB3-type monomers were prepared from nontoxic natural gallic acid and amino acids. These monomers were then melt-polycondensed in the presence of MgO as a catalyst via a transesterification process at 170-190 degrees C to yield the hyperbranched poly(ester-amide)s bearing terminal acetyl groups. FTIR and NMR spectra confirmed the structures of all the monomers and polymers. The degrees of branching, estimated from 1H NMR and quantitative 13C NMR spectra, were 0.50-0.68. These hyperbranched polymers displayed moderately high molecular weights. Hydrolytic and enzymatic degradation studies were carried out in vitro at 37.5 degrees C in NaOH hydrotropic solution and in Tris-HCl buffer (pH = 8.6) containing proteinase K, respectively. The results indicate that the hyperbranched poly(ester-amide)s are degradable hydrolytically as well as enzymatically, and the rate of hydrolytic degradation increases with the pH value of the solution.     

Blends of aliphatic polyesters. VI. Lipase-catalyzed hydrolysis and visualized phase structure of biodegradable blends from poly(epsilon-caprolactone) and poly(L-lactide)

Phase-separated biodegradable polymer blends were prepared from poly(epsilon-caprolactone) (PCL) and poly(L-lactide) (PLLA), and Rhizopus arrhizus lipase-catalyzed hydrolysis and phase structure of the blend films were investigated. Gravimetry revealed that the lipase-catalyzed hydrolysis of PCL in PCL- and PLLA-rich phases is disturbed by the presence of PLLA. Polarimetry confirmed the occurrence of a predominant hydrolysis of PCL and subsequent removal of the hydrolyzed water-soluble PCL oligomers in the blend films. Gravimetry and gel permeation chromatography of the non-blended PLLA film indicated that R. arrhizus lipase has no catalytic effect on the hydrolysis of PLLA. The phase structure of the blend films could be visualized by selective enzymatic removal of one component and subsequent scanning electron microscopic observation.     

Compatibilization effect of poly(epsilon-caprolactone)-b-poly(ethylene glycol) block copolymers and phase morphology analysis in immiscible poly(lactide)/poly(epsilon-caprolactone) blends

The miscibility and phase behavior of two stereoisomer forms of poly(lactide) (PLA: poly (L-lactide) (PLLA) and poly(DL-lactide) (PDLLA)) blends with poly(epsilon-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) and PCL-b-monomethoxy-PEG (PCL-b-MPEG) block copolymers have been investigated by differential scanning calorimetry (DSC). The DSC thermal behavior of both the blend systems revealed that PLA is miscible with the PEG segment phase of PCL-b-(M)PEG but is still immiscible with its PCL segment phase although PCL was block-copolymerized with PEG. On the basis of these results, PCL-b-PEG was added as a compatibilizer to PLA/PCL binary blends. The improvement in mechanical properties of PLA/PCL blends was achieved as anticipated upon the addition of PCL-b-PEG. In addition, atomic force microscopy (AFM) measurements have been performed in order to study the compositional synergism to be observed in mechanical tests. AFM observations of the morphological dependency on blend composition indicate that PLA/PCL blends are immiscible but compatible to some extent and that synergism of compatibilizing may be maximized in the compositional blend ratio before apparent phase separation and coarsening.     

Fluorescence studies on the complex formation between poly(rA) containing 1,N6-ethenoadenosine and poly(rU)

The interaction of the 1,N6-etheno derivatives of poly(rA) (poly(epsilon rA] with poly(rU) has been studied by absorption and fluorescence spectroscopy. The stoichiometry of the interaction is found to be 1 epsilon A:1 rU and 1 epsilon A:2 rU as well as in the case of poly(rA)-poly(rU) interaction. The fluorescence properties, including the intensity and polarization of fluorescence, respond to the conformational transition of poly(epsilon rA)-poly(rU) complexes. The introduction of epsilon A groups into poly(rA) results in a marked decrease in the melting temperature, suggesting that epsilon A may destabilize the helical structure. The three-exponential decay law obtained with poly(epsilon rA)-poly(rU) complexes indicates the existence of at least three different stacked conformational states.     

An amperometric biosensor based on hemoglobin immobilized in poly(epsilon-caprolactone) film and its application

In this study, poly(varepsilon-caprolactone) (PCL) was synthesized using the varepsilon-caprolactone (CL) monomer ring-opening polymerization. We demonstrated that the hemoglobin (Hb) entrapped in PCL film could retain its original conformation by FT-IR spectra. A pair of well-defined redox peaks with a formal potential (E0') of about -0.38V (vs. SCE) in a pH 7.0 phosphate buffer solution was obtained at the Hb-PCL film modified GC electrode. The dependence of [Formula: see text] on the pH of the buffer solution indicated that the conversion of heme Fe(III)/Fe(II) was a reaction of one electron coupled to one proton. The apparent heterogeneous electron transfer rate constants (ks) of Hb confined to PCL was valuated as (18.7+/-0.8)s(-1) according to Laviron's equation. The surface concentration (Gamma*) of the electroactive Hb in the PCL film was estimated to be (7.27+/-0.57)x10(-11)molcm(-2). The Hb-PCL film modified electrode was shown to be an excellent amperometric sensor for the detection of hydrogen peroxide. The linear range is from 2 to 30microM with a detection limit of 6.07x10(-6)M. The sensor was effectively testified by the determination of the hydrogen peroxide in eyedrops as real samples.     

Biodegradable amphiphilic copolymers based on poly(epsilon-caprolactone)-graft chondroitin sulfate as drug carriers

The goal of this study was to develop a new type of core-shell micelles based on biocompatible and biodegradable amphiphilic copolymers, named PCL-CS, using chondroitin sulfate (CS) as a hydrophilic segment and poly(epsilon-caprolactone) (PCL) as a hydrophobic segment. The copolymers, prepared from the various compositions between CS and PCL, were characterized by Fourier transform infrared spectrometer, proton nuclear magnetic resonance spectrometer, and differential scanning calorimeter. The PCL-CS copolymers could be assembled into micelles using a simple emulsion. With the fluorescent probe technique, the critical micelle concentrations were obtained in the range of 1.26 x 10(-3)-8.86 x 10(-3) mg/mL. The spherical images of micelles were visualized in the presence of polyvinyl alcohol (PVA) with the use of the transmission electron microscope. The particle sizes of micelles were all smaller than 300 nm, neither aggregate nor change in hydrodynamic sizes after 15 days staying in solutions containing salts or PVA by dynamic light scattering. The intracellular uptake of KB cells incubated with PCL-CS micelles was evidenced by confocal laser scanning microscope upon loading fluorescein isothiocyanate labeled bovine serum albumin as a probe.     

Synthesis and micellization of amphiphilic brush-coil block copolymer based on poly(epsilon-caprolactone) and PEGylated polyphosphoester

A novel biodegradable amphiphilic brush-coil block copolymer consisting of poly(epsilon-caprolactone) and PEGylated polyphosphoester was synthesized by ring opening polymerization. The composition and structure of the copolymer were characterized by 1H NMR, 13C NMR, and FT-IR, and the molecular weight and molecular weight distribution were analyzed by gel permeation chromatograph (GPC) measurements to confirm the diblock structure. These amphiphilic copolymers formed micellar structures in water, and the critical micelle concentrations (CMCs) were around 10(-3) mg/mL, which was determined using pyrene as a fluorescence probe. Transmission electron microscopy (TEM) images showed that the micelles took an approximately spherical shape with core-shell structure, which was further demonstrated by laser light scattering (LLS) technique. The degradation behavior of the polymeric micelle was also investigated in the presence of Pseudomonas lipase and characterized by GPC measurement. Such polymer micelles from brush-coil block copolymers are expected to have wide utility in the field of drug delivery.     

Novel biodegradable and pH-sensitive poly(ester amide) microspheres for oral insulin delivery

Biodegradable and pH-sensitive PEAs based on dual amino acids are designed, synthesized, and characterized. Insulin can be loaded into the PEA microspheres by a solid-in-oil-in-oil technique with high encapsulation efficiency. The feasibility of PEA microspheres as oral insulin delivery carriers is evaluated in vitro and in vivo. The hydrophobic leucine groups on PEA seem to play an important role in the pH-dependent release mechanism and cytotoxicity of PEA microspheres. Oral administration of insulin-loaded PEA microspheres to streptozotocin-induced diabetic rats at 60 IU kg(-1) is able to reduce fasting plasma glucose levels to 49.4%. These results indicate that PEA microspheres are potential new vehicles for insulin oral delivery.     

Impact of silicone-based block copolymer surfactants on the surface and bulk microscopic organization of a biodegradable polymer,poly(epsilon-caprolactone)

Two amphiphilic AB block copolymers, containing a highly compatible poly(epsilon-caprolactone) (PCL) block connected to a poly(dimethylsiloxane) (PDMS) block having a low surface energy, are synthesized and characterized in terms of their dispersion in a presynthesized PCL matrix. X-ray photoelectron spectroscopy, contact angle measurements, atomic force microscopy, and optical microscopy are used to describe the evolution of the surface chemical composition, as well as the surface and bulk morphology of the PCL/copolymer blends as a function of the nature and weight surface free energy and the dispersion of the copolymers in the blends, leading to important modifications of the bulk and the surface morphology. These differences are interpreted in terms of the impact of the block copolymers on the semicrystalline polymer structure and related properties in the prospect of using the surfactants to improve the synthesis of PCL in supercritical CO(2).     

Formation of and coalescence from the inclusion complex of a biodegradable block copolymer and alpha-cyclodextrin. 2: A novel way to regulate the biodegradation behavior of biodegradable block copolymers

A biodegradable block copolymer (PCL-b-PLLA, M(n) = 1.72 x 10(4), M(w)/M(n) = 1.37) of poly(epsilon-caprolactone) (PCL) and poly(L-lactide) (PLLA) with very low crystallinity was obtained by forming the inclusion complex between alpha-cyclodextrin molecules and PCL-b-PLLA followed by coalescence of the guest polymer chains. Films of the as-synthesized and coalesced copolymer samples, PCL and PLLA homopolymers of approximately the same chain lengths as the corresponding blocks of PCL-b-PLLA, and a physical blend of PCL/PLLA homopolymers with the same molar composition as PCL-b-PLLA were prepared by melt-compression molding between Teflon plates. Subsequently, the in vitro biodegradation behavior of these films was studied in phosphate buffer solution containing lipase from Rhizopus arrhizus, by means of ultraviolet spectra, attenuated total reflectance FTIR spectra, differential scanning calorimetry, wide-angle X-ray diffraction measurements, and weight loss analysis. PCL segments were found to degrade much faster than PLLA segments, both in the pure state and in copolymer or blend samples. Consistent with our expectation, suppression of the phase separation, as well as a decrease of crystallinity, in the coalesced copolymer sample led to a much faster enzymatic degradation than that of either as-synthesized copolymer or the PCL/PLLA physical blend sample, especially during the early stages of biodegradation. Thus the biodegradation behavior of biodegradable block copolymers, which is of decisive importance in drug delivery and controlled release systems, may be regulated by the novel and convenient means recently reported by us.(1)     

A convenient method for the synthesis of amine-terminated poly(ethylene oxide) and poly(epsilon-caprolactone)

A convenient synthetic route to prepare amine-terminated poly(ethylene oxide) (PEO) and poly(epsilon-caprolactone) (PCL) was described. The strategy involved two-step reactions, the condensation of hydroxyl-terminated PEO and PCL with N-benzyloxycarbonyl amino acid followed by the catalytic hydrogenation under mild conditions. NMR and GPC measurements indicated that the reactions proceeded nearly quantitatively. Amine-terminated PEO thus prepared was used to initiate the polymerization of alpha-(N(epsilon)-benzyloxycarbonyl-L-lysine) N-carboxy anhydride [lys(Z)-NCA], and the results confirmed that the reactivity of the amino group was high.     

Self-assembled micelles of biodegradable triblock copolymers based on poly(ethyl ethylene phosphate) and poly(-caprolactone) as drug carriers

A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.     

Grafting of cellulose fibers with poly(epsilon-caprolactone) and poly(L-lactic acid) via ring-opening polymerization

In this study, ring-opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL) and L-lactide (L-LA) has been performed from cellulose fibers. The hydroxyl groups on cellulose act as initiators in the polymerization, and the polymers are covalently bonded to the cellulose fiber. As an attempt to introduce more available hydroxyl groups on the surface, and thereby obtain higher grafting efficiency in the ROP of epsilon-CL and L-LA, unmodified paper was modified with xyloglucan-bis(methylol)-2-methylpropanamide (XG-bis-MPA) and 2,2-bis(methylol)propionic acid (bis-MPA), respectively. The grafted substrates were characterized via Fourier transform infrared spectroscopy (FTIR), contact angle measurement, atomic force microscopy, and enzymatic degradation. The results showed a successful grafting of poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLLA) from the cellulose fiber surfaces. Furthermore, the results showed an improved grafting efficiency after activation of the cellulose surface with bis-MPA, and showed that the amount of grafted polymer could be controlled by the ratio of added free initiator to monomer.     

Anaerobic biodegradation of aliphatic polyesters: poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) and poly(epsilon-caprolactone)

Poly(3-hydroxybutyrate-co-3-hydroxyoctanoate), PHBO, represents a class of PHA copolymers that contain both short-chain-length and medium-chain-length repeat units. Radiolabeled and cold PHBO, containing 90 mol % 3-hydroxybutyrate and 10 mol % 3-hydroxyoctanoate were chemically synthesized using a new difunctional alkoxyzinc initiator. (14)C-PHBO was incubated with samples of anaerobic digester sludge, septage, freshwater sediment, and marine sediment under conditions resembling those in situ. In addition, it was incubated in laboratory-scale landfill reactors. (14)C-PCL (poly-epsilon-caprolactone) was incubated with anaerobic digester sludge and in landfill reactors. Biodegradation was determined by measuring generation of (14)CO(2) and (14)CH(4) resulting from mineralization of the radiolabeled polymers. PHBO was extensively mineralized in digester sludge, septage sediments, and the landfill reactors, with half-lives less than 30 days. PCL was not significantly mineralized in digester sludge over 122 days. In the landfill reactors, PCL mineralization was slow and was preceded by a long lag period (>200 days), suggesting that PCL mineralization is limited by its rate of hydrolysis. The results indicate that PHBO is practically biodegradable in the major anaerobic habitats that it may enter. In contrast, anaerobic biodegradation of PCL is less ubiquitous and much slower.     

Fabrication of biodegradable poly(ester-amide)s based on tyrosine natural amino acid

N,N′-Bis[2-(methyl-3-(4-hydroxyphenyl)propanoate)]isophthaldiamide (5), a novel diol monomer containing chiral group, was prepared by the reaction of S-tyrosine methyl ester (3) with isophthaloyl dichloride (4a). A new family of optically active and potentially biodegradable poly(ester-amide)s (PEAs) based on tyrosine amino acid were prepared by the polycondensation reaction of diol monomer 5 with several aromatic diacid chlorides. The resulting new polymers were obtained in good yields with inherent viscosities ranging between 0.25 and 0.42 dL/g and are soluble in polar aprotic solvents. They showed good thermal stability and high optical purity. The synthetic compounds were characterized and studied by FT-IR, ¹H-NMR, specific rotation, elemental and thermogravimetric analysis (TGA) techniques and typical ones by ¹³C-NMR, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) analysis. Soil burial test of the diphenolic monomer 5, and obtained PEA6a, and soil enzymatic assay showed that the synthesized diol and its polymer are biologically active and probably biodegradable in soil environment.     

Two interconverting pentaiodide forms in the cyclomaltohexaose (alpha-cyclodextrin) polyiodide inclusion complex with sodium ion: dielectric and Raman spectroscopy studies

The polycrystalline inclusion complex of cyclomaltohexaose, (alpha-CD)(2) x NaI(5) x 8H(2)O, has been investigated via dielectric spectroscopy over a frequency range of 0-100 kHz and the temperature range of 125-450 K. Additionally, a Raman spectroscopy study was accomplished in the temperature ranges of (i) 153-298 K and (ii) 303-413 K. The ln sigma versus 1/T variation revealed the order-disorder transition of some normal hydrogen bonds to those of a flip-flop type at 200.9 K. From 278.3 up to 357.1K, the progressive transformation (H(2)O)(tightly bound)-->(H(2)O)(easily movable) takes place resulting in an Arrhenius linear increment of the ac-conductivity with activation energy E(a)=0.32 eV. In the range of 357.1-386.1K a second linear part with E(a)=0.55 eV is observed, indicating the contribution of sodium ions via the water-net.The rapid decrease of the ac-conductivity at T>386.1K is due to the removal of the water molecules from the crystal lattice, whereas the abrupt increase at T>414.9 K is caused by the sublimation of iodine.The Raman bands at 160 and 169 cm(-1) indicate the coexistence of (I(2) x I(-) x I(2)) and (I3(-) x I(2)<-->I(2) x I3(-)) units, respectively.The (I3(-) x I(2)<-->I(2) x I3(-)) units are presented as form (I), and their central I(-) ion is disordered in occupancy ratio different from 50/50 (e.g., ...60/40...70/30...).The(I(2) x I(-) x I(2)) units are displayed by the 2 equiv forms (IIa) and (IIb). In (IIa) the central I(-) ion is twofold disordered in an occupancy ratio of 50:50, whereas in (IIb) the central I(-) ion is well-ordered and equidistant from the two I(2) molecules. At low temperatures the transformation (I)-->(IIa) takes place, whereas at high temperatures the inverse one (IIa)-->(I) happens. X-ray powder diffraction and Rietveld analysis revealed a triclinic crystal form with space group P1 and lattice parameters that are in good agreement with the theoretical values.     

FT-IR imaging spectroscopy of phase separation in blends of poly(3-hydroxybutyrate) with poly(L-lactic acid) and poly(epsilon-caprolactone)

The detection of phase separation and identification of miscibility in biopolymer blends is an important aspect for the improvement of their physical properties. In this article, the phase separation in blends of poly(3-hydroxybutyrate) (PHB) with poly(L-lactic acid) (PLA) and poly(epsilon-caprolactone) (PCL), respectively, has been studied as a function of the blend composition by FT-IR imaging spectroscopy. For both polymer blend systems, a miscibility gap has been found around the 50:50% (w/w) composition of the two components. Furthermore, the separating phases have been identified as blends of the two polymer components and their compositions could be determined from calibrations based on the spectra of the blends in the compositional range of miscibility. The data derived from FT-IR spectroscopic imaging were corroborated by additional DSC analyses and mechanical stress-strain measurements of polymer blend films, which exhibited a characteristic fracture behavior as a function of PHB composition.     

Mechanical grinding effect on thermodynamics and inclusion efficiency of loratadine-cyclodextrin inclusion complex formation

The interaction of poor water-soluble drug loratadine (LOR) with β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous or solid state was investigated. Mechanical grinding effect on the inclusion steps, thermodynamic kinetics and inclusion efficiency of inclusion complex formation of LOR with β-CD or HP-β-CD was quantitatively investigated by DSC and FT-IR microspectroscopy with curve-fitting analysis. The phase solubility profiles of LOR with β-CD and HP-β-CD were classified as A_L-type phase diagram. The grinding-induced reduction in LOR crystallinity in the presence of β-CD or HP-β-CD was found to be apparent zero-order kinetics. The inclusion efficiency of solid inclusion complex for LOR/β-CD or LOR/HP-β-CD was significantly correlated with the reduction in LOR crystallinity and the grinding time. The mechanism of inclusion complex formation for LOR/β-CD or LOR/HP-β-CD was proposed through the progressive reduction in LOR crystallinity, the promoted LOR amorphization, and molecular inclusion processes in the continuous energy input process of mechanical grinding.