Syntheses of poly(lactic acid)‐poly(ethylene glycol) serial biodegradable polymer materials via direct melt polycondensation and their characterization

Directly starting from lactic acid (LA) and poly(ethylene glycol) (PEG), biodegradable material polylactic acid‐polyethylene glycol (PLEG) was synthesized via melt copolycondensation. The optimal synthetic conditions, including prepolymerization method, catalyst kinds and quantity, copolymerization temperature and time, LA stereochemical configuration, feed weight ratio m_LA/m_PEG and M_n of PEG, were all discussed in detail. When D ,L ‐LA and PEG (M_n = 1000 Da) prepolymerized together as feed weight ratio m_{D ,l‐LA}/m_PEG = 90/10, 15 h copolycondensation under 165°C and 70 Pa, and 0.5 wt % SnO as catalyst, gave D ,L ‐PLEG1000 with the highest [η] of 0.40 dL/g, and the corresponding MW was 41,700 Da. Using L ‐LA instead of D ,L ‐LA, 10 h polymerization under 165°C and 70 Pa, and 0.5 wt % SnO as catalyst, gave L ‐PLEG1000 with the highest [η] of 0.21 dL/g and MW of 15,600 Da. Serial D ,L ‐PLEG with different feed weight ratio and M_n of PEG were synthesized via the simple and practical direct melt copolycondensation, and characterized with FTIR, ¹H NMR, GPC, DSC, XRD, and contact angle testing. D ,L ‐PELG not only had higher MW than PDLLA, PLLA and L ‐PELG, but also better hydrophilicity than PDLLA. The novel one‐step method could be an alternative route to the synthesis of hydrophilic drug delivery carrier PLEG instead of the traditional two‐step method using lactide as intermediate. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 577–587, 2006     

Synthesis of poly(D,L‐lactic acid) modified by triethanolamine by direct melt copolycondensation and its characterization

Using D ,L ‐lactic acid (LA) and multifunctional group compound triethanolamine (TEA) as starting materials, a novel biodegradable material poly(D ,L ‐lactic acid‐triethanolamine) [P(LA‐TEA)] was directly synthesized by simpler and practical melt polycondensation. The appropriate synthetic condition was discussed in detail. When the molar feed ratio LA/TEA was 30/1, the optimal synthesis conditions were as follows: a prepolymerization time of 12 h; 0.5 weight percent (wt %) SnO catalyst; and melt copolycondensation for 8 h at 160°C, which gave a novel star‐shaped poly(D,L ‐lactic acid) (PDLLA) modified by TEA with the maximum intrinsic viscosity [η] 0.93 dL g⁻¹. The copolymer P(LA‐TEA) as a different molar feed ratio was characterized by [η], Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H‐NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). Increasing the molar feed ratio of LA/TEA, T_g and M_w increased. However, all copolymers were amorphous, and their T_g (12.2°C–32.5°C) were lower than that of homopolymer PDLLA. The biggest M_w was 9400 Da, which made the biodegradable polymer be potentially used as drug delivery carrier, tissue engineering material, and green finishing agent in textile industry. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Studies on the synthesis and thermal properties of copoly(L‐lactic acid/glycolic acid) by direct melt polycondensation

A two‐step direct copolymerization process of L ‐lactic acid (L ‐LA)/glycolic acid (GA) was developed. The first step was to produce an oligomer of L ‐LA/GA and then the oligomer was polymerized with binary catalyst tin chloride dihydrate/p‐toluenesulfonic acid. In this way, the copoly(L ‐LA/GA) (PLGA), without any organic solvent, was synthesized directly. The thermal properties and solubility in chloroform of PLGA were studied by DSC and NMR. The results showed that the melting point of PLGA decreases with increasing mole fraction of GA units in copolymer. In addition, the melting point of polymer also decreased with increasing degree of racemization of polymer. The solubility of PLGA in chloroform decreased with the increase of the average lengths of the glycolic acid units. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2163–2168, 2004     

Synthesis and structure control of l‐lactic acid–glycolic acid copolymer by homo‐copolymerization

A two‐step direct melt copolymerization process of l ‐lactic acid (L ‐LA)/glycolic acid (GA) was developed: poly(l ‐lactic acid) (PLLA) and poly(glycolic acid) (PGA) with different molecular weight was first synthesized respectively by binary catalyst (tin chloride/p‐toluenesulfonic or tin chloride); and then poly(l ‐lactic‐co‐glycolic acid) (b‐PLGA) was produced by melt polymerization of the as‐prepared PLLA and PGA, wherein the composition and chain structure of b‐PLGA copolymers could be controlled by the molecular weight of PLLA. The chain structure and thermal properties of copolymers were studied by Wide‐angle X‐ray diffraction, nuclear magnetic resonance, differential scanning calorimetry, and thermogravimetric analysis. In comparison with the random PLGA (r‐PLGA) synthesized by one‐step direct melt polymerization, the average l ‐lactic blocks length (L_LA) in b‐PLGA was longer while the average glycolic blocks length (L_GA) in b‐PLGA was shorter which further resulted in the improved crystallinity and thermostability. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41566.     

Synthesis of poly(D,L‐lactic acid) modified by cholic acid via direct melt copolycondensation and its characterization

From D,L ‐lactic acid and the natural functional molecule cholic acid (CA), the biodegradable material poly(D,L ‐lactide–cholate) was synthesized via direct copolycondensation. For the CA/lactic acid (LA) molar feed ratio of 1/64, the optimal synthesis conditions were as follows: a prepolymerization time of 8 h, 0.3 wt % SnO catalyst, and melt copolycondensation for 8 h at 160°C, which gave a novel star‐shaped poly(D,L ‐lactic acid) (PDLLA) modified by CA with the maximum weight‐average molecular weight of 5600 Da at a yield of 51.9%. The copolymer poly(D,L ‐lactide–cholate) at different molar feed ratios was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, thermogravimetry, and X‐ray diffraction. Decreasing the molar feed ratio of CA/LA from 1/15 to 1/128 reduced the average number of CA units embedded in the copolymer from 4 to 1. With 1/15 CA/LA, the copolymer was not a star‐shaped polymer, and its weight‐average molecular weight was the biggest (weight‐average molecular weight = 12,700 Da, weight‐average molecular weight/number‐average molecular weight = 1.68). With 1/32 CA/LA, the copolymer with two CA units was not a star‐shaped polymer either. With 1/64, 1/100, and 1/128 CA/LA, the copolymer mainly had one CA unit core embedded as a normal star‐shaped PDLLA with four arms, and certain crystallinity could be detected. The novel direct copolycondensation method was simple and practical for the synthesis of the asymmetrical star‐shaped PDLLA material, and it was advantageous for this PDLLA material embedded in the special bioactive molecule CA to be applied in the field of drug delivery and tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Evaluation of blood compatibility of MeO‐PEG‐poly (D,L‐lactic‐co‐glycolic acid)‐PEG‐OMe triblock copolymer

The aim of the present work was to assess the blood compatibility of monomethoxy (polyethylene glycol)‐poly (D ,L ‐lactic‐co‐glycolic acid)‐monomethoxy (polyethylene glycol) (MeO‐PEG‐PLGA‐PEG‐OMe, PELGE) triblock copolymer as a propriety material for intravenous use in vitro. Three different proportional triblock copolymers were synthesized. According to the International Standard Organization (ISO) and US Pharmacopoeia XXIII recommendations, siliconized glass tube was used as the negative control sample, while nonsiliconized glass tube was used as the positive control. The blood compatibility of the films of poly (D ,L ‐lactic and glycolic acid) (PLGA) was evaluated by dynamic clotting time, activated partial thromboplastin time (APTT), and plasma recalcification time (PRT) measurements, platelet adhesion investigation, and hemolytic ratio analysis. The results revealed that blood compatibility of the materials was good. Nanoparticles made by this kind of materials might be promising for intravenous use. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1019–1023, 2006     

Synthesis and characterization of biodegradable low molecular weight aliphatic polyesters and their use in protein‐delivery systems

Poly(lactic acid) (PLA) and poly(lactic‐co‐GA) (PLGA) with low molecular weights were synthesized by a one‐step polycondensation of lactic acid (LA) with glycolic acid (GA) molecules using stannous octoate as a catalyst at 160°C. A high yield (>80%) of all the polymers was obtained in the study. The PLA and PLGA copolymers were characterized by ¹H‐NMR, GPC, and DSC measurements, etc. We elaborated HSA‐loaded microspheres based on PLA and PLGA copolymers with different monomer ratios (LA/GA = 85:15, 75:25, 65:35, and 50:50) by the solvent‐extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of the morphology, size, and encapsulation efficiency (E.E.). The highest E.E. (69.3%) of HSA was obtained for HSA‐loaded PLGA (65/35) microspheres among all the formulations. In vitro matrix degradation and protein release of these microspheres were performed in phosphate‐buffer saline (PBS; 154 mM, pH 7.4). The degradation profiles were characterized by measuring the loss of the microsphere mass and the decrease of the polymer intrinsic viscosity. The release profiles were investigated from the measurement of the protein presented in the release medium at various intervals. It was shown that the matrix degradation and protein‐release profiles were highly LA/GA ratio‐dependent. It is suggested that these matrix polymers may be optimized as carriers in protein‐ and peptide‐delivery systems for different purposes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1848–1856, 2004     

Biodegradations of statistical copolymers composed of D,L‐lactide and cyclic carbonates

Syntheses and biodegradation of statistical copolymers of D ,L ‐lactide (D ,L ‐LA) with trimethylene carbonate (TMC), rac‐1‐methyltrimethylene carbonate (1‐MTMC) and 2,2‐dimethyltrimethylene carbonate (2,2‐DTMC) were investigated at various monomer ratios using SmMe(C₅Me₅)₂THF as an initiator at 80 °C for 24 h in toluene. Biodegradations of poly(D ,L ‐LA‐co‐racemo‐1‐MTMC) (95/5) and poly(D ,L ‐LA‐co‐2,2‐DTMC) (98/2) with a compost at 60 °C proceed rapidly. Enzymatic degradations of these polymers were also performed using cholesterol esterase, lipoprotein lipase and proteinase K. Only poly(D ,L ‐LA‐co‐TMC) was biodegraded with cholesterol esterase, while poly(TMC), poly(1‐MTMC), poly(2,2‐DTMC) and poly(D ,L ‐LA) were barely degraded with these enzymes. Biodegradations of poly(D ,L ‐LA‐co‐TMC) (87/13) and poly(D ,L ‐LA‐co‐racemo‐1‐MTMC) (95/5) are rapid using proteinase K. Physical properties of these copolymers were also described. © 2003 Society of Chemical Industry     

生物降解材料PLGA50的直接法合成与表征

分别以外消旋乳酸(D,L-LA)和左旋乳酸(L-LA)为原料,通过与乙醇酸(GA)熔融共聚[n(GA):n(LA)=1:1],直接合成了生物降解材料聚(乳酸-乙醇酸)(PLGA50)。用特性黏度[鏬、凝胶渗透色谱(GPC)、傅立叶红外光谱(FTIR)、核磁共振氢谱(1H　NMR)、差热分析(DSC)、X-射线衍射、接触角测试等手段,对PLGA50的相对分子质量、结构、性能等进行了系统的表征。PLGA50为无定型高分子,相同合成条件下D,L-PLGA50的相对分子质量比L-PLGA50高,其亲水性能比外消旋聚乳酸(PDLLA)有所改善。     

Water‐assisted formation of honeycomb films of poly(L‐lactic‐co‐glycolic acid)

The ordered honeycomb structures of poly(L ‐lactic‐co‐glycolic acid) and poly(D ,L ‐lactic‐co‐glycolic acid) fabricated in a humid atmosphere were reported in this paper. It was found that surfactants were important in the formation of honeycomb films of hydrophobic polymer. The affecting factors, such as the environment temperature, the atmosphere humidity, and the concentration of the polymer solution of the honeycomb porous structure, were also tested. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1013–1018, 2006     

Zinc‐based catalyst for the ring‐opening polymerization of cyclic esters

A zinc‐based catalyst zinc bis[bis(trimethylsilyl)amide] was used for the polymerization of cyclic esters including L ‐lactide (L ‐LA) and 2‐methyl‐2‐carboxyl‐propylene carbonate (MBC). The polymerization of L ‐lactide in THF could be carried out successfully under mild conditions in very short time by using the zinc catalyst and alcohols as the initiators. Kinetic study in solution polymerization prooved the polymerization has high monomer conversion degree close to 100% and the molecular weight of the resulting polyester has linear increase with the increase of [M]₀ /[I] (molar ratio of monomer to initiator). Sequential polymerization of L ‐LA and MBC in THF also showed high MBC conversion of 94% with a narrow molecualr weight maintained, indicating a living nature of this polymerization. The zinc catalyst system has also been used for the L ‐LA bulk polymerization with a high monomer conversion. ¹³C NMR indicated the polymer possesses high regioregularity and the minor regioirregular component was owing to the D ‐LA in the monomer inserted into the polymer mainchain during the transesterifcation. Interaction between monomer and zinc catalyst has been found to be a key factor to sustain a homogenous solution during the initiating procedure. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

The ring‐opening polymerization of D,L‐lactide catalyzed by new complexes of Cu,Zn, Co,and Ni Schiff base derived from salicylidene and L‐aspartic acid

D ,L ‐lactide (LA) was first successfully ring‐opening polymerized in melt by Schiff base complexes K[ML]nH₂O [M = Cu(II), Zn(II), Co(II), Ni(II); n = 2, 2, 3, 3.5; H₃L = L‐aspartic acid‐salicylidene Schiff base], which were prepared by Schiff base ligand derived from salicylidene and L‐aspartic acid and corresponding acetates. The effects of various complexes, the molar ratio of K[ML]nH₂O/LA, the polymerization temperature, and time were studied in detail. The results show that all complexes studied have the ability to initiate the ring‐opening polymerization of D ,L ‐lactide in melt. More than 90% high polymerization conversion and narrow molecular weight distribution (MWD) can be obtained very easily. However, the Ni(II) complex shows better catalytic property than other complexes on the polymerization and the molecular weight (MW) of poly(D ,L ‐lactide) (PLA) produced. With a rise in temperature and a prolongation of time, the MW of PLA decreased remarkably. The MW of PLA prepared by all complexes is not very high, which might be related to the crystalline water of complexes. X‐ray study indicated that PLA produced by Ni(II) complex is an amorphous polymer. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3312–3315, 2002     

Design,synthesis, and characterization of a potential flame retardant poly(lactic acid‐co‐pyrimidine‐2,4,5,6‐tetramine) via direct melt polycondensation

Directly starting from d ,l ‐lactic acid (LA) and pyrimidine‐2,4,5,6‐tetramine (PTA), the copolymer P(LA‐co‐PTA) as a novel potential solid compatible polymeric flame retardant is synthesized as designed via melt polycondensation. When the molar feed ratio LA/PTA is 60/1, the optimal synthetic conditions are discussed. After the prepolymerization at 140°C for 8 h, using 0.5 wt % stannous oxide as the catalyst, the melt copolymerization at 160°C for 4 h gives the copolymer with the biggest intrinsic viscosity 0.88 dL g^?1. The structures and properties of P(LA‐co‐PTA)s at different molar feed ratios are characterized by FT‐IR, ¹H‐NMR, ¹³C‐NMR, GPC, XRD, DSC, and TGA. The decomposition temperatures of P(LA‐co‐PTA)s are higher than these of homopolymer poly(d,l ‐lactic acid) (PDLLA). All copolymers have higher char yield than PDLLA, and the more PTA in the feed content, the higher char yield. What's more, there are some residues at 700–800°C, indicating that P(LA‐co‐PTA)s have good charring ability. When the monomer PTA is introduced into polylactic acid by chemical bonding as purine (PU) unit formed during the condensation, both the PTA's relatively higher nitrogen content and the PU's similar structure with flame retardant benzimidazole are beneficial to improve the thermal stability and charring ability, especially the latter. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40275.     

Synthesis and characterization of the biomaterial poly(lactic acid‐co‐Nε‐carbobenzoyloxy‐L‐lysine) via direct melt copolymerization

With D,L ‐lactic acid and N^ϵ‐carbobenzoyloxy‐L ‐lysine [Lys(Z)] as the starting monomer material and tin dichloride as the catalyst, the drug carrier material poly(lactic acid‐co‐N^ϵ‐carbobenzoyloxy‐L ‐lysine) was synthesized via direct melt polycondensation. The copolymer was systematically characterized with intrinsic viscosity testing, Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, and X‐ray diffraction. The influences of different feed molar ratios were examined. With increasing molar feed content of Lys(Z), the intrinsic viscosity, weight‐average molecular weight, and polydispersity index (weight‐average molecular weight/number‐average molecular weight) gradually decreased. Because of the introduction of Lys(Z) with a big aromatic ring into the copolymer, the glass‐transition temperature gradually increased with increasing feed charge of Lys(Z), and all of the copolymers were amorphous. The copolymers, with weight‐average molecular weights from 10,500 to 6900 Da, were obtained and could reach the molecular weight level of poly(lactic acid) modified by Lys(Z) via the ring‐opening polymerization of the cyclic intermediates, such as lactide and morpholine‐2,5‐dione. However, a few terminal carboxyl groups might have been deprotected during the polymerization reaction under high temperatures. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Glass transition and mechanical properties of PLLA and PDLLA‐PGA copolymer blends

The change of the glass transition temperatures (T_g) in the blend of poly(L ‐lactic acid) (PLLA) and the copolymers of poly(D,L ‐lactic acid) and poly(glycolic acid) (PDLLA‐PGA) with different D,L ‐lactic acid and glycolic acid composition ratio (50 : 50, 65 : 35, and 75 : 25) was studied by DSC. Dynamic mechanical measurement and tensile testing were performed at various temperatures around T_g of the blend. In the blend of PLLA and PDLLA‐PGA50 (composition ratio of PDLLA and PGA 50 : 50), T_g decreased from that of PLLA (about 58°C) to that of PDLLA‐PGA50 (about 30°C). A single step decrease was observed in the DSC curve around T_g between the weight fraction of PLLA (W(PLLA)) 1.0 and 0.7 (about 52°C) but two‐step changes in the curve are observed between W(PLLA) = 0.6 and 0.3. The T_g change between that of PLLA and that of PDLLA‐PGA and the appearance of two T_gs suggest the existence of PLLA rich amorphous region and PDLLA‐PGA copolymer rich amorphous region in the blend. A single step decrease of E′ occurs at around T_g of the pure PLLA but the two‐step decrease was observed at W(PLLA) = 0.6 and 0.4, supporting the existence of the PLLA rich region and PDLLA‐PGA rich region. Tensile testing for various blends at elevated temperature showed that the extension without yielding occurred above T_g of the blend. Partial miscibility is suggested for PLLA and PDLLA‐PGA copolymer blends. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2164–2173, 2004     

Synthesis and characterization of degradable copoly(trans‐4‐hydroxy‐L‐proline/ϵ‐caprolactone)

The melt polycondensation reaction of N‐protected trans‐4‐hydroxy‐L ‐proline (N‐Z‐Hpr) and ?‐caprolactone (?‐CL) over a wide range of molar fractions in the feed produced new and degradable poly(N‐Z‐Hpr‐co‐?‐CL)s with stannous octoate as a catalyst. The optimal reaction conditions for the synthesis of the copolymers were obtained with 1.5 wt % stannous octoate at 140°C for 24 h. The synthesized copolymers were characterized by IR spectrophotometry, ¹H NMR, differential scanning calorimetry, and Ubbelohde viscometry. The values of the inherent viscosity (η_inh) and glass‐transition temperature (T_g) of the copolymers depended on the molar fractions of N‐Z‐Hpr. With an increase in the trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline (N‐CBz‐Hpr) feed from 10 to 90 mol %, a decrease in η_inh from 2.47 to 1.05 dL/g, and an increase in T_g from ?48 to 49°C were observed. The in vitro degradation of these poly(N‐CBz‐Hpr‐co‐?‐CL)s was evaluated from weight‐loss measurements. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 3176–3182, 2003     

Stereocontrolled Synthesis and Pharmacological Evaluation of Azetidine‐2,3‐Dicarboxylic Acids at NMDA Receptors

The four stereoisomers of azetidine‐2,3‐dicaroxylic acid (L ‐trans‐ADC, L ‐cis‐ADC, D ‐trans‐ADC, and D ‐cis‐ADC) were synthesized in a stereocontrolled fashion following two distinct strategies: one providing the two cis‐ADC enantiomers and one giving access to the two trans‐ADC enantiomers. The four azetidinic amino acids were characterized in a radioligand binding assay ([³H]CGP39653) at native NMDA receptors: L ‐trans‐ADC showed the highest affinity (K_i=10 μM ) followed by the D ‐cis‐ADC stereoisomer (21 μM ). In contrast, the two analogues L ‐cis‐ADC and D ‐trans‐ADC were low‐affinity ligands (>100 and 90 μM , respectively). Electrophysiological characterization of the ADC compounds at the four NMDA receptor subtypes NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D expressed in Xenopus oocytes showed that L ‐trans‐ADC displayed the highest agonist potency at NR1/NR2D (EC₅₀=50 μM ), which was 9.4‐, 3.4‐, and 1.9‐fold higher than the respective potencies at NR1/NR2A–C. D ‐cis‐ADC was shown to be a partial agonist at NR1/NR2C and NR1/NR2D with medium‐range micromolar potencies (EC₅₀=720 and 230 μM , respectively). A subsequent in silico ligand–protein docking study suggested an unusual binding mode for these amino acids in the agonist binding site.     

Synthesis and characterization of biodegradable linear–hyperbranched barbell‐like poly(ethylene glycol)‐supported poly(lactic‐ran‐glycolic acid) copolymers through direct polycondensation

A series of biodegradable linear–hyperbranched barbell‐like poly(ethylene glycol) (PEG)‐supported poly(lactic‐ran‐glycolic acid) (PLGA) copolymers were synthesized with PEG, d ,l ‐lactic acid aqueous solution, glycolic acid and gluconic acid (Glu) under bulk conditions. The branching density of the hyperbranched section was varied by controlling the molar ratio of Glu to hydroxyl‐terminal groups of PEG ([Glu]/[OH] = 1, 3.5, 6.0, 8.5). Chemical structures of these copolymers were confirmed using NMR spectroscopy. The molecular weights were determined using ¹H NMR group analysis and gel permeation chromatography, both results being consistent with one another. The results of hydrolytic degradation indicate that these copolymers can degrade completely in no more than three weeks. The thermal properties were evaluated using differential scanning calorimetry and thermogravimetric analysis. The results indicate that the glass transition temperatures and melt temperatures of these copolymers are not above 50 °C. The self‐assembly behavior of the copolymers on hydrophilic surfaces was also investigated. The morphology of self‐assembly films made of the copolymers was observed using atomic force microscopy, and the results indicate that these copolymers exhibit more inhomogeneous and rough structural orientated films on a silicon wafer substrate with increasing branching densities. Due to the favorable biodegradability and biocompatibility of the PLGA and PEG, the results suggest new possibilities for these novel structural amphiphilic linear–hyperbranched barbell‐like copolymers as potential biomaterials. © 2013 Society of Chemical Industry     

Amphiphilic PLGA-PEG-PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid

Different compositional parameters of poly(_D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol) triblock copolymers (PLGA-PEG) were varied to analyze their effect on gel formation and mechanical properties. Parameters such as hydrophilic/hydrophobic ratio (PLGA/PEG ratio), lactic acid/glycolic acid ratio (LA/GA ratio), PEG molecular weight (PEG Mw), polymer solution concentration, copolymer molecular weight (Mw), and polydispersity index (PDI) were studied in this work. For copolymers with PEG Mw of 1500 Da, gelation temperature (34–37 °C) was affected by _D,L-LA/GA ratio and Mw; while modulus was affected by LA/GA ratio, Mw, and Mn. Based on the parametric study, an injectable, thermoresponsive hyaluronic acid (HA) delivery platform was designed for ocular applications. PLGA-PEG copolymers with _D,L-LA/GA ratio of 15/1, PLGA/PEG ratio of 2/1, PEG Mw of 1500 Da, and Mw of about 6 KDa gelled at 35 °C, were optically transparent, had a modulus less than 350 Pa and were used for HA release studies. This work also demonstrates, for the first time, an extended and controlled release of HA, beyond 2 weeks, from injectable hydrogels modified with a noncovalent interacting agent, poly(L-lysine). Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the nonmodified hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48678.     

Preparation of high‐molecular‐weight poly(L‐lactic acid)‐based polymers through direct condensation polymerization in bulk state

Poly(L ‐lactic acid‐co‐succinic acid‐co‐1,4‐butanediol) (PLASB) was synthesized by a direct condensation copolymerization of L ‐lactic acid, succinic acid (SA), and 1,4‐butanediol (BD) in bulk state using titanium(IV) butoxide (TNBT) as a catalyst. Weight average molecular weight (M_w) of PLASB increased from 3.5 × 10⁴ to 2.1 × 10⁵ as the content of SA and BD went up from 0.01 to 0.5 mol/100 mol of L ‐lactic acid (LA). PLASB having M_w in the range from 1.8 × 10⁵ to 2.1 × 10⁵ showed tensile properties comparable to those of commercially available poly(L ‐lactic acid) (PLLA). In sharp contrast, homopolymerization of LA in bulk state produced PLLA with M_w as low as 4.1 × 10⁴, and it was too brittle to prepare specimens for the tensile tests. M_w of PLASB synthesized by using titanium(IV)‐2‐ethyl(hexoxide), indium acetate, indium hydroxide, antimony acetate, antimony trioxide, dibutyl tin oxide, and stannous‐2‐ethyl 1‐hexanoate was compared with that of PLASB obtained by TNBT. Ethylene glycol oligomers with different chain length were added to LA/SA in place of BD to investigate effect of chain length of ethylene glycol oligomers on the M_w of the resulting copolymers. Biodegradability of PLASB was analyzed by using the modified Sturm test. Toxicity of PLASB was evaluated by counting viable cell number of mouse fibroblast cells that had been in contact with PLASB discs. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 466–472, 2006