A spectroscopic study of the self-association and inter-molecular aggregation behaviour of pH-responsive poly(l-lysine iso-phthalamide)

The pH mediated intra-molecular association and inter-molecular aggregation of a range of amphiphilic poly(l-lysine iso-phthalamide) polymers have been investigated in aqueous solution over a range of pH values and concentrations. The desired functionality of these novel bioresponsive amphiphilic polymers was achieved by incorporating pendant hydrophilic carboxyl groups along the polymer backbone, via the l-lysine moiety, balanced by a degree of hydrophobicity introduced via the iso-phthaloyl moiety. Incorporation of low levels of bis-functional Cy3 (poly-Cy3) and/or Cy5 dye (poly-Cy3/5 or poly-Cy5) co-monomers in the responsive polymer backbone allowed detailed probing of the pH mediated hydrophobic association using a combination of optical spectroscopic techniques. Both steady-state fluorescence spectroscopy and fluorescence lifetime measurements of poly-Cy3 revealed a conformational transition at pH 4.5. Thus, below a critical pH the polymer collapsed into a compact globular structure (hypercoil) bringing the fluorophore molecules into close proximity with one another. This resulted in a dramatic reduction in fluorescence intensity and fluorescent lifetime in the single fluorophore systems (poly-Cy3) accompanied by a red shift in the maximum emission wavelength. Observed redshifts in the emission maxima and enhancements of fluorescent lifetimes with increasing polymer concentration suggested the formation of polymer aggregates. Fluorescence resonance energy transfer (FRET) was measured in mixtures of single fluorophore containing poly-Cy3 (donor) and poly-Cy5 (acceptor) and dual fluorophore containing poly-Cy3 (donor)/Cy5 (acceptor) in an effort to distinguish between intra-molecular versus inter-molecular association. The relevance of the results with respect to potential in vivo applications (drug delivery and biodiagnostics) is discussed.     

Amorphous cell studies of polyglycolic, poly(l-lactic), poly(l,d-lactic) and poly(glycolic/l-lactic) acids

In this paper static amorphous state properties (solubility parameter, free volume (using the Voorintholt method and the Voronoi tessellations) and pair correlation functions, the last ones also by including water molecules in the cells), which can be related to the probability for water uptake, have been studied for polyglycolic (PGA), poly(l-lactic) (PLLA), poly(l,d-lactic) (PLLA/PDLA) and poly(glycolic/l-lactic) (PGA/PLLA) acids, known to be biodegradable polymers. The polymer consistent force field, as modified by the authors, has been used in the calculations. The main purpose of this paper is to investigate, which of the amorphous state properties would be relevant for water uptake. We also discuss the validity of th6e methods used for these kinds of studies, and the related reliability of the computed results. Chain flexibilities of the studied polyesters in the amorphous phase have been analyzed, and the intermolecular interactions are found to cause the most significant variations in the distributions of the adjacent chain dihedral angle pairs and in the related populations of the low-energy regions of the comonomers. The solubility parameters, as calculated from the cohesion energy densities of the constructed models, suggest PGA being most compatible with water, in agreement with experiments. On the other hand, the quantitative structure-property relationships method ‘Synthia’ suggests a very similar solubility in water for all particular polyesters. In the PLAs and PGA/PLLA, however, a larger number of hydrogen bonds is formed between the water molecules and the carbonyl oxygen atoms of the chains showing a better possibility of PLLA and its copolymers to break into shorter chains. As an explanation, the hydrophobic methyl groups of the lactide units are suggested to push the water molecules closer to the carbonyl groups than in homo-PGA.     

Controlled crystal nucleation in the melt-crystallization of poly(l-lactide) and poly(l-lactide)/poly(d-lactide) stereocomplex

Among the various inorganic nucleators examined, Talc and an aluminum complex of a phosphoric ester combined with hydrotalcite (NA) were found to be effective for the melt-crystallization of poly(l-lactide) (PLLA) and PLLA/poly(d-lactide) (PDLA) stereo mixture, respectively. NA (1.0 phr (per one hundred resin)) can exclusively nucleate the stereocomplex crystals, while Talc cannot suppress the homo crystallization of PLLA and PDLA in the stereo mixture. Double use of Talc and NA (in 1.0 phr each) is highly effective for enhancing the crystallization temperature of the stereo complex without forming the homo crystals. The stereocomplex crystals nucleated by NA show a significantly lower melting temperature (207 °C) than the single crystal of the stereocomplex (230 °C) in spite of recording a large heat of crystallization ΔH_c (54 J/g). Photomicrographic study suggests that the spherulites with a symmetric morphology are formed in the stereo mixture added with NA while the spherulites do not grow in size in the mixture added with Talc. The exclusive growth of the stereocomplex crystals by the melt-crystallization process will open a processing window for the PLLA/PDLA.     

Synthesis and characterization of poly(l-glutamic acid)-block-poly(l-phenylalanine)

Poly(γ-benzyl l-glutamate)-block-poly(l-phenylalanine) was prepared via the ring opening polymerization of γ-benzyl l-glutamate N-carboxyanhydride and l-phenylalanine N-carboxyanhydride using n-butylamine·HCl as an initiator for the living polymerization. Polymerization was confirmed by ¹H-nuclear magnetic resonance spectroscopy and matrix assisted laser desorption ionization time of flight mass spectroscopy. After deprotection, the vesicular nanostructure of poly(l-glutamic acid)-block-poly(l-phenylalanine) particles was examined by transmission electron microscopy and dynamic light scattering. The pH-dependent properties of the nanoparticles were evaluated by means of ζ-potential and transmittance measurements. The results showed that the block copolypeptide could be prepared using simple techniques. Moreover, the easily prepared PGA-PPA block copolypeptide showed pH-dependent properties due to changes in the PGA ionization state as a function of pH; this characteristic could potentially be exploited for drug delivery applications.     

Miscibility and properties of linear poly(l-lactide)/branched poly(l-lactide) copolyester blends

Polymer blends consisting of linear poly(l-lactide) (PLLA) and different proportions of dendritic PLLA-based copolyesters (hb-PLLA) characterized by different degrees of branching (DB) were obtained in melt. The solid-state properties of poly(l-lactide)s and their blends were investigated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), atomic force microscopy (AFM) and stress-strain measurements. DSC and DMA methods proved miscibility of PLLA/hb-PLLA blends for the studied composition range. AFM indicated that no phase separation occurs in PLLA/hb-PLLA blends and that PLLA and hb-PLLA cocrystallize in one single lamellae type. The mechanical characteristics of PLLA/hb-PLLA blends deteriorated with an increase of the DB and with changing blend composition. Susceptibility of the blends to biodegradation was studied by measuring the weight loss in two different biodegradation media. PLLA/hb-PLLA blends showed more pronounced hydrophilic character and higher susceptibility to biodegradation with an increase in the degree of branching.     

Transcrystalline structures of poly(l-lactide)

Poly(l-lactide) (PLLA) film containing transcrystalline (TC) structures can easily be obtained by placing PLLA films melted between two poly(tetrafluoroethylene) (PTFE) sheets, followed by isothermal crystallization at 122 °C. The fine structures of the PLLA-TC film were studied by various structural techniques such as X-ray diffractometry, optical microscopy and transmission electron microscopy. We also examined the purification effect upon the morphology of PLLA-TC film. The formation of the TC structures revealed that one-dimensional spherulitic growth occurred from the assembling impurities as nucleation agent near the PTFE substrate in the heterogeneous nucleation system. We found that the b-axis of PLLA crystal was parallel to the lamellae growth direction confirmed using X-ray diffraction. The precipitated PLLA film crystallized in a similar process exhibited scanty TC textures, suggesting that the existence of impurity in the PLLA sample was an important factor for the formation of those structures.     

Thermal degradation of poly(l-lactide): effect of alkali earth metal oxides for selective l,l-lactide formation

To achieve the feed stock recycling of poly(l-lactide) (PLLA) to l,l-lactide, PLLA composites including alkali earth metal oxides, such as calcium oxide (CaO) and magnesium oxide (MgO), were prepared and the effect of such metal oxides on the thermal degradation was investigated from the viewpoint of selective l,l-lactide formation. Metal oxides both lowered the degradation temperature range of PLLA and completely suppressed the production of oligomers other than lactides. CaO markedly lowered the degradation temperature, but caused some racemization of lactide, especially in a temperature range lower than 250 °C. Interestingly, with MgO racemization was avoided even in the lower temperature range. It is considered that the effect of MgO on the racemization is due to the lower basicity of Mg compared to Ca. At temperatures lower than 270 °C, the pyrolysis of PLLA/MgO (5 wt%) composite occurred smoothly causing unzipping depolymerization, resulting in selective l,l-lactide production. A degradation mechanism was discussed based on the results of kinetic analysis. A practical approach for the selective production of l,l-lactide from PLLA is proposed by using the PLLA/MgO composite.     

Preparation and properties of optically active poly(N-methacryloyl l-leucine methyl ester)

Reported in this paper is the effect of varying initiator, catalyst, ligand, solvent, and temperature on atom transfer radical polymerization (ATRP) of N-methacryloyl l-leucine methyl ester (MALM). Optimized polymerization conditions involve tris[2-(dimethylamino)ethyl]amine (Me₆TREN) as ligand, CuBr as catalyst, methyl 2-bromopropionate as initiator, and toluene or benzene as solvent. Under these conditions the PMALM samples produced possess tunable molecular weight and low polydispersity. Also reported are results of PMALM characterization by differential scanning calorimetry (DSC), thermogravimetry, and polarimetry.     

Crystallization behavior of poly(l-lactic acid)

The crystallization behavior of poly(l-lactic acid) was studied in the range of 80-160 °C. The peak crystallization time (τ_p) was defined and obtained from the crystallization isotherm measured with a differential scanning calorimeter (DSC). Isothermal crystallization temperature (T_c) dependence of log(τ_p) discretely changed at 113 °C (= T_b). The linear growth rate of spherulite, G, was measured with a polarizing microscope. The T_c dependence of G and the size of the spherulite also discretely changed at T_b. Crystal structures for samples isothermally crystallized at temperatures which were higher and lower than T_b were orthorhombic (α-form) and trigonal (β-form), respectively. The discrete change of the crystallization behavior was explained by the formation of different crystal.     

Preparation of multi-walled carbon nanotubes grafted with synthetic poly(l-lysine) through surface-initiated ring-opening polymerization

A surface-initiated ring-opening polymerization approach was used to functionalize multi-walled carbon nanotubes (MWNTs) with linear poly(l-lysine) (PLL). The oxidized MWNTs, which resulted from the treatment of MWNTs with mixed concentrated sulfuric acid and nitric acid, were converted into amino-functionalized MWNTs (MWNT-NH₂) by the amidation of carboxylic group on MWNT surface with excess 1,6-diaminohexane. Surface-initiated ring-opening polymerization of ?-(benzyloxycarbonyl)-l-lysine N-carboxyanhydride with MWNT-NH₂ as the initiator resulted in MWNTs grafted with poly(?-(benzyloxycarbonyl)-l-lysine) (MWNT-g-PLys(Z)). After the acidolysis of benzylcarbamate group of the grafting poly(?-(benzyloxycarbonyl)-l-lysine) chain, water-soluble MWNTs grafted with PLL (MWNT-g-PLL) were obtained. The successful grafting was confirmed by Fourier transform infrared spectroscopy, thermal gravimetric analysis, X-ray photoelectron spectroscopy, elemental analyses, high-resolution transmission electron microscopy (HRTEM) and field-emission scanning electron microscopy. HRTEM indicates that MWNTs were enveloped by PLL layer. The as-prepared MWNT-g-PLys(Z) and MWNT-g-PLL exhibited excellent ability to disperse homogeneously in THF and water, respectively.     

Carbodiimide-mediated synthesis of poly(l-lactide)-based networks

Poly(l-lactide-co-succinic anhydride) networks were synthesised via the carbodiimide-mediated coupling of poly(l-lactide) (PLLA) star polymers. When 4-(dimethylamino)pyridine (DMAP) alone was used as the catalyst, gelation did not occur. However, when 4-(dimethylamino)pyridinium p-toluenesulfonate (DPTS), the salt of DMAP and p-toluenesulfonic acid (PTSA), was the catalyst, the networks obtained had gel fractions comparable to those which were reported for networks synthesised by conventional methods. Greater gel fractions and conversion of the prepolymer terminal hydroxyl groups were observed when the hydroxyl-terminated star prepolymers reacted with succinic anhydride in a one-pot procedure than when the hydroxyl-terminated star prepolymers reacted with presynthesised succinic-terminated star prepolymers. The thermal properties of the networks, glass transition temperature (T_g), melting temperature (T_m) and crystallinity (X_c) were all strongly influenced by the average molecular weights between the crosslinks (). The network with the smallest (1400 g/mol) was amorphous and had a T_g of 59 °C while the network with the largest (7800 g/mol) was 15% crystalline and had a T_g of 56 °C.     

Formation of banded and non-banded poly(l-lactic acid) spherulites during crystallization of films of poly(l-lactic acid)/poly(ethylene oxide) blends

In this study, a series of poly(l-lactic acid) (PLLA)/poly(ethylene oxide) (PEO) blends with different PLLA concentrations was prepared. Films of these blends crystallized with and without a coverslip were characterized by the presence and absence of banded structures, respectively. This difference in morphology was observed because the PEO component of the blends was oxidized at a high temperature (125 °C) in air without the protection of a coverslip. X-ray photoelectron spectroscopy (XPS) results showed that the surface of the blends crystallized in nitrogen without a coverslip contained mostly PLLA while the surfaces of the same blends crystallized under a coverslip contained only a moderately higher concentration of PLLA than their bulks. The migration of PLLA to the surface of the blends during crystallization in nitrogen when no coverslip was used was due to its low surface tension. Phase images obtained using atomic force microscopy (AFM) indicated that the banded structures consisted of valleys and ridges, which were in fact flat-on and edge-on lamellae, respectively. A detailed time-of-flight secondary ion mass spectrometry (ToF-SIMS) examination suggested that PLLA and PEO were located mainly on the surfaces of the ridges and valleys, respectively.     

Synthesis and characterization of poly(ethylene glycol)-b-poly (l-lactide)-b-poly(l-glutamic acid) triblock copolymer

A biodegradable amphiphilic triblock copolymer of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-glutamic acid) (PEG-b-PLLA-b-PLGA) was obtained by catalytic hydrogenation of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(γ-benzyl-l-glutamic acid) (PEG-b-PLLA-b-PBLGA) synthesized by the ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl-l-glutamate (BLG-NCA) with amino-terminated MPEG-b-PLLA-NH₂ as a macroinitiator. MPEG-b-PLLA-NH₂ converted from MPEG-b-PLLA-OH first reacted with tert-Butoxycarbonyl-l-phenylalanine (Phe-^NBOC) and dicyclohexylcarbodiimide (DCC) and then deprotected the tert-butoxycarbonyl group. MPEG-b-PLLA-OH was prepared by ROP of l-lactide with monomethoxy poly(ethylene glycol) in the presence of stannous octoate. The triblock copolymer and its diblock precursors were characterized by ¹H NMR, FTIR, GPC and DSA (drop shape analysis) measurements. The lengths of each block polymers could be tailored by molecular design and the ratios of feeding monomers. The triblock polymer PEG-b-PLLA-b-PLGA containing carboxyl groups showed obviously improved hydrophilic properties and could be a good potential candidate as a drug delivery carrier.     

Plasticization of semicrystalline poly(l-lactide) with poly(propylene glycol)

Plasticization of semicrystalline poly(l-lactide) (PLA) with a new plasticizer - poly(propylene glycol) (PPG) is described. PLA was plasticized with PPG with nominal M_w of 425 g/mol (PPG4) and 1000 g/mol (PPG1) and crystallized. The plasticization decreased T_g, which was reflected in a lower yield stress and improved elongation at break. The crystallization in the blends was accompanied by a phase separation facilitated by an increase of plasticizer concentration in the amorphous phase and by annealing of blends at crystallization temperature. The ultimate properties of the blends with high plasticizer contents correlated with the acceleration of spherulite growth rate that reflected accumulation of plasticizer in front of growing spherulites causing weakness of interspherulitic boundaries. In PLA/PPG1 blends the phase separation was the most intense leading to the formation of PPG1 droplets, which facilitated plastic deformation of the blends that enabled to achieve the elongation at break of about 90-100% for 10 and 12.5 wt% PPG1 content in spite of relatively high T_g of PLA rich phase of the respective blends, 46.1-47.6 °C. Poly(ethylene glycol) (PEG), long known as a plasticizer for PLA, with nominal M_w of 600 g/mol, was also used to plasticize PLA for comparison.     

Stereocomplex crystallization and spherulite growth behavior of poly(l-lactide)-b-poly(d-lactide) stereodiblock copolymers

The non-isothermally and isothermally crystallized stereodiblock copolymers of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) with equimolar l-lactyl and d-lactyl units and different number-average molecular weights (M_n) of 3.9 × 10³, 9.3 × 10³, and 1.1 × 10⁴ g mol⁻¹, which are abbreviated as PLLA-b-PDLA copolymers, contained only stereocomplex crystallites as crystalline species, causing higher melting temperatures of the PLLA-b-PDLA copolymers compared to those of PLLA homopolymers. In the case of non-isothermal crystallization, the cold crystallization temperatures of the PLLA-b-PDLA copolymers during heating and cooling were respectively lower and higher than those of PLLA homopolymers, indicating accelerated crystallization of PLLA-b-PDLA copolymers. In the case of isothermal crystallization, in the crystallizable temperature range, the crystallinity (X_c) values of the PLLA-b-PDLA copolymers were lower than those of the PLLA homopolymers, and were susceptible to the effect of crystallization temperature in contrast to that of homopolymers. The radial growth rate of the spherulites (G) of the PLLA-b-PDLA copolymers was the highest at the middle M_n of 9.3 × 10³ g mol⁻¹. This trend is different from that of the PLLA homopolymers where the G values increased monotonically with a decrease in M_n, but seems to be caused by the upper critical M_n values of PLLA and PDLA chains as in the case of PLLA/PDLA blends (in other papers), above which homo-crystallites are formed in addition to stereocomplex crystallites. The disturbed crystallization of PLLA-b-PDLA copolymers compared to that of the PLLA/PDLA blend is attributable to the segmental connection between the PLLA and PDLA chains, which interrupted the free movement of those chains of the PLLA-b-PDLA copolymers during crystallization. The crystallite growth mechanism of the PLLA-b-PDLA copolymers was different from that of the PLLA/PDLA blend.     

Unique crystallization behavior of poly(l-lactide)/poly(d-lactide) stereocomplex depending on initial melt states

A unique crystallization behavior of poly(l-lactide) (PLLA)/poly(d-lactide) (PDLA) stereocomplex was observed when a PLLA/PDLA blend (50/50) was subjected to specific melting conditions. PLLA and PDLA were synthesized by ring opening polymerization of l- or d-lactide using zinc lactate as catalyst. PLLA/PDLA blend was prepared through solution mixing followed by vacuum drying. The blend was melted under various melting conditions and subsequent crystallization behaviors were analyzed by using DSC, XRD, NMR and ESEM. Stereocomplex was exclusively formed from the 50/50 blend of PLLA and PDLA with relatively low molecular weights. Surprisingly, stereocomplex crystallization was distinctly depressed when higher melting temperature and longer melting period were applied, in contrast to homopolymer crystallization. Considering predominant interactions between PLLA and PDLA chains, a novel model of melting process is proposed to illustrate this behavior. It is assumed that PLLA and PDLA chain couples would preserve their interactions (melt memory) when the stereocomplex crystal melts smoothly, thus resulting in a heterogeneous melt which can easily crystallize. The melt could gradually become homogeneous at higher temperature or longer melting time. The strong interactions between PLLA and PDLA chain segments are randomly distributed in a homogeneous melt, thus preventing subsequent stereocomplex crystallization. However, the homogeneous melt can recover its ability to crystallize via dissolution in a solvent.     

Effect of the addition of poly(d-lactic acid) on the thermal property of poly(l-lactic acid)

Thermal property and crystallization behavior of PLLA blended with a small amount of PDLA (1-5 wt%) were studied. PDLA molecules added in PLLA formed stereocomplex crystallites in the PLLA matrix. When the blend was cooled to a temperature below T_m of PLLA, stereocomplex crystallites acted as nucleation sites of PLLA and enhanced the crystallization of PLLA significantly (heterogeneous nucleation). Such crystallization enhancement was not observed when the blend with lower PDLA content was cooled from 240 °C at which both PLLA crystal and the stereocomplex disappeared. Low molecular weight PDLA isolated in the matrix of PLLA did not form a stereocomplex crystallite with a large surface area enough to act as a nucleation site. On the other hand, high molecular weight PDLA chains formed a large stereocomplex crystallite. With increasing PDLA content, stereocomplex crystallites were more easily formed and they acted as nucleation sites. PLLA crystal near the stereocomplex crystallites has an incomplete structure and showed a melting peak at a lower temperature than pure PLLA crystal.     

Formation of poly(l,d-lactide) spheres with controlled size by direct dialysis

In this work, we show that simple dialysis of a poly(dl-lactic acid) (PLA) solution against water resulted in the spontaneous formation of PLA spheres. We observed initial formation of particles with irregular shape and large size, which then were disrupted into uniform and smooth nanospheres. Further, the formation process of PLA spheres was also investigated by dynamic light scattering technique (DLS) in situ. Based on these experimental results, it was proposed that the PLA spheres were formed in three steps: (1) aggregation - individual PLA chains got aggregated with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA spheres. In addition, the size of the spheres could be well controlled by the preparation conditions such as the speed of dialysis, initial solvent, initial water content and polymer concentration. The ease with which these spheres could be fabricated and the ability to control the size of spheres should facilitate investigations of their scope for drug delivery.     

Crystallization and morphology of stereocomplexes in nonequimolar mixtures of poly(l-lactic acid) with excess poly(d-lactic acid)

Crystallization of nonequimolar compositions of poly(d-lactic acid) with low-molecular-weight poly(l-lactic acid) (PDLA/LM_w-PLLA) blends leads to formation of various fractions of stereocomplexed PLA (sc-crystallites) and homocrystallites (PDLA or PLLA). For the PDLA/LM_w-PLLA blends within the composition window of LM_w-PLLA content between 30 and 50 wt%, only sc-crystal exists and no homocrystal is present. On the other hand, for PDLA/LM_w-PLLA blends with excess PDLA, e.g. PDLA/LM_w-PLLA = 90/10, atomic-force microscopy (AFM) characterization on various stages of crystallization of sc-PLA crystal with PDLA homocrystal shows a repetitive stacking of excess PDLA on pre-formed sc-PLA crystal serving as crystallizing templates. The crystallization initially begins with string-like (fibril-like) PDLA lamellae, followed with PDLA aggregating on sc-PLA crystal into a bead-on-string crystal, then growing to thicker irregularly-shaped dough-like lamellae. Repetitive growth cycle from strings to bead-on-string lamellae continues on top of the dough-like lamellae as new substrates, until ending impingement of the PDLA spherulites.     

Crystallization of poly(l-lactide-dimethyl siloxane-l-lactide) triblock copolymers and its effect on morphology of microphase separation

This investigation characterizes the molten morphologies following isothermal crystallization of poly(l-lactide-block-dimethyl siloxane-block-l-lactide) triblock copolymers, which were synthesized by ring-opening polymerization of l-lactide using hydroxyl-telechelic PDMS as macroinitiators, via small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). The break-out and preservation of the nanostructure of the triblock copolymer depended on the segregation strength, which was manipulated by varying the degree of polymerization. The crystallization kinetics of these semicrystalline copolymers and the effect of isothermal crystallization on their melting behaviors were also studied using DSC, FT-IR and WAXS. The exclusive presence of α-phase PLLA crystallite was verified by identifying the absence of the WAXS diffraction signal at 2θ = 24.5° and the presence of IR absorption at 1749 cm⁻¹ when the PLLA segment of the block copolymers was present as a minor component. The dependence of the crystallization rate (Rc) on the chemical composition of the triblock copolymers reveals that the Rc of the triblock copolymers was lower than that of PLLA homopolymer and the Rc were substantially reduced when the minor component of the crystallizable PLLA domains was dispersed in the PDMS matrix.