Fully bio‐based poly(ɛ‐capolactone)/poly(lactide) alternating multiblock supramolecular polymers: Synthesis,crystallization behavior,and properties

Supramolecular poly(?‐capolactone)/poly(lactide) alternating multiblock copolymers were prepared by UPy‐functionalized poly(lactide)‐b‐ poly(?‐capolactone)‐b‐ poly(lactide) copolymers. The prepared supramolecular polymers (SMPs) exhibit the characteristic properties of thermoplastic elastomers. The stereo multiblock SMPs (sc‐SMPs) were formed by blending UPy‐functionalized poly(l ‐lactide)‐b‐ PCL‐b‐ poly(l ‐lactide) (l ‐SMPs) and UPy‐functionalized poly(d ‐lactide)‐b‐ PCL‐b‐ poly(d ‐lactide) (d ‐SMPs) due to stereocomplexation of the PLLA and PDLA blocks. Sc‐SMPs with low content of d ‐SMPs (≤20%) are transparent, elastic solids, while those having high d ‐SMPs content are opaque, brittle solids. The effects of l ‐SMPs/d ‐SMPs mixing ratios on thermal, crystallization behaviors, crystal structure, mechanical and hydrophilic properties of sc‐SMPs were deeply investigated. The incorporation of UPy groups depresses the crystallization of polymer, and the stereocomplex formation accelerates the crystallization rate. The used initiator functionalized polyhedral oligomeric silsesquioxanes causes a different effect on the crystallization of PLA and PCL blocks. The tensile strength and elongation at break of l _d /d _d ‐SMPs (d represents the initiator diethylene glycol) are significantly larger than that of l _p /d _p ‐SMPs (p represents the initiator polyhedral oligomeric silsesquioxanes), and their heat resistance and hydrophilicity can be also modulated by the l ‐SMPs/d ‐SMPs mixing ratios and the different initiators. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45575.     

Influence of racemization on stereocomplex‐induced gelation of water‐soluble polylactide–poly(ethylene glycol) block copolymers

Ring‐opening polymerization of L ‐ or D ‐lactide was realized at 140 °C for a period of 7 days in the presence of dihydroxyl poly(ethylene glycol) (PEG), with M?_n = 4000 g mol^?1, using zinc lactate as initiator. The resulting poly(L ‐lactide)–PEG–poly(L ‐lactide) and poly(D ‐lactide)–PEG–poly(D ‐lactide) triblock copolymers are water soluble with polylactide (PLA) block length ranging from 11 to 17 units. Both the tube inverting method and rheological measurements were used to evaluate the gelation properties of aqueous solutions containing single copolymers or L /D copolymer pairs. Stereocomplexation between poly(L ‐lactide) and poly(D ‐lactide) blocks is observed for mixed solutions. Hydrogel formation is detected in the case of relatively long PLA blocks (DP _PLA = 17), but not for copolymers with shorter PLA blocks (DP _PLA = 11–13) due to partial racemization of L ‐lactyl units. Racemization is largely reduced when the reaction time is shortened to 1 day. Under these conditions, DP _PLA of 8 is sufficient for the stereocomplexation of PLA–PEG block copolymers, and DP _PLA above 10 leads to the formation of hydrogels of PLA–PEG block copolymers. On the other hand, racemization appears as a general phenomenon in the (co)polymerization of L ‐lactide with Zn(Lac)₂ as initiator, although it is negligible or undetectable in the case of high molar mass polymers. Therefore, racemization is the limiting factor for the stereocomplexation‐induced gelation of water‐soluble PLA–PEG block copolymers where the PLA block length generally ranges from 10 to 30. Reaction conditions including initiator, time and temperature should be strictly controlled to minimize racemization. Copyright © 2010 Society of Chemical Industry     

Effect of multi‐branched PDLA additives on the mechanical and thermomechanical properties of blends with PLLA

Stereocomplex formation between poly(l ‐lactic acid) (PLLA) and poly(d ‐lactic acid) (PDLA) in the melt state was investigated and altered via the addition of multi‐branched poly(d ‐lactide) (PDLA) additives. Two different multi‐branched PDLA additives, a 3‐arm and 4‐arm star‐shaped polymeric structure, were synthesized as potential heat resistance modifiers and incorporated into PLLA at 5, 10, and 20 (w/w) through melt blending. Mechanical and thermomechanical properties of these blends were compared with linear poly(l ‐lactide) (PLLA) as well as with blends formed by the addition of two linear PDLA analogs that had similar molecular weights to their branched counterparts. Blends with linear PDLA additives exhibited two distinct melting peaks at 170–180°C and 200–250°C which implied that two distinct crystalline domains were present, that of the homopolymer and that of the stereocomplex, the more stable crystalline structure formed by the co‐crystallization of both d ‐ and l ‐lactide enantiomers. In contrast, blends of PLLA with multi‐branched PDLA formed a single broad melting peak indicative of mainly formation of the stereocomplex, behavior which was confirmed by X‐ray diffraction (XRD) analysis. The heat deflection temperature determined by thermal mechanical analysis was improved for all blends compared to neat PLLA, with increases of up to180°C for 20% addition of the 3‐arm PLLA additive. Rheological properties of the blends, as characterized by complex viscosity (η*), remained stable over a wide temperature range. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 132, 42858.     

Effect of the melt‐mixing condition on the physical property of poly(l‐lactic acid)/poly(d‐lactic acid) blends

The effect of the mixing condition in a mill‐type mixer on the thermal property and the crystal formation of the poly(l ‐lactide)/poly(d ‐lactide) blends is investigated. The blends melt‐mixed at 200 and 210 °C under application of a high shear flow tend to show a single melting peak of the stereocomplex crystal (SC) in the differential scanning calorimetry first and second heating processes without indicating the trace of the melting of homo‐chiral crystal. The mixing at an elevated temperature causes a serious thermal degradation. Further kneading of the blends at an elevated temperature higher than T_m of SC causes the transesterification between the same enatiomeric chains forming block copolymers of l ‐ and d ‐chains. This block copolymer acts as a nucleating agent of SC and the compatibilizing agent between poly(l ‐lactide) and poly(d ‐lactide) and promotes the formation of SC. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45489.     

Preparation and characterization of nanohydroxyapatite strengthening nanofibrous poly(L‐lactide) scaffold for bone tissue engineering

A biomimetic nanofibrous poly(L ‐lactide) scaffold strengthened by nanohydroxyapatite particles was fabricated via a thermally induced phase separation technique. Scanning electron microscopy results showed that nanohydroxyapatite particles uniformly dispersed in the nanofibrous poly(L ‐lactide) scaffold (50–500 nm in fiber diameter) with slight aggregation at a high nHA content, but showed no influence on the interconnected macroporous and nanofibrous structure of the scaffold. The nanofibrous poly(L ‐lactide) scaffold presented a specific surface area of 34.06 m² g^?1, which was much higher than that of 2.79 m² g^?1 for the poly(L ‐lactide) scaffold with platelet structure. Moreover, the specific surface area of the nanofibrous scaffold was further enhanced by incorporating nanohydroxyapatite particles. With increasing the nanohydroxyapatite content, the compressive modulus and amount of bovine serum albumin adsorbed on the surface of the nanofibrous composite scaffold were markedly improved, as opposed to the decreased crystallinity. In comparison to poly(L ‐lactide) scaffold, both the nanofibrous poly(L ‐lactide) and poly(L ‐lactide)/nanohydroxyapatite scaffolds exhibited a faster degradation rate for their much larger specific surface area. The culture of bone mesenchymal stem cell indicated that the composite nanofibrous poly(L ‐lactide) scaffold with 50 wt % nanohydroxyapatite showed the highest cells viability among various poly(L ‐lactide)‐based scaffolds. The strengthened biomimetic nanofibrous poly(L ‐lactide)/nanohydroxyapatite composite scaffold will be a potential candidate for bone tissue engineering. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Design and synthesis of biodegradable copolyester poly(ε‐caprolactone‐co‐d,l‐lactide) with four pendent functional groups

A novel biodegradable copolyester poly(ε‐caprolactone‐co‐d ,l ‐lactide) with four pendent functional groups was designed and synthesized. The synthetic route includes the following three steps: (1) synthesis of OH‐terminated PCLA (PCLA‐OH) by the ring‐opening copolymerization of ε‐caprolactone and d ,l ‐lactide; (2) end‐group functionalization of PCLA‐OH through the esterification with lysine; and (3) synthesis of tetra‐amino‐terminated PCLA (PCLA‐NH₂) by removing the protecting groups. The composition, structure, and thermal property of these copolyesters were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and modulated differential scanning calorimetry. Results revealed that the molecular weight and glass transition temperature of PCLA‐NH₂ can be tailored by the careful selection of synthesis parameters. Moreover, polyester elastomers based on PCLA‐NH₂ were synthesized and characterized. These polyester elastomers are stabilized in their rubbery state in room temperature and exhibit tunable physiochemical and mechanical properties. POLYM. ENG. SCI., 54:2170–2176, 2014. © 2013 Society of Plastics Engineers     

Effect of poly(l‐lactide)/poly(d‐lactide) block length ratio on crystallization behavior of star‐shaped asymmetric poly(l(d)‐lactide) stereoblock copolymers

Effect of Poly(l ‐lactide)/Poly(d ‐lactide) (PLLA/PDLA) block length ratio on the crystallization behavior of star‐shaped poly(propylene oxide) block poly(d ‐lactide) block poly (l ‐lactide) (PPO–PDLA–PLLA) stereoblock copolymers with molecular weights (M_n) ranging from 6.2 × 10⁴ to 1.4 × 10⁵ g mol^?1 was investigated. Crystallization behaviors were studied utilizing differential scanning calorimetry (DSC), polarized optical microscopy (POM), and wide‐angle X‐ray diffraction (WAXD). Only stereocomplex crystallites formed in isothermal crystallization at 140 to 156°C for all samples. On one hand, the overall crystallization rate decreased as PLLA/PDLA block length ratio increased. As PLLA/PDLA block length ratio increased from 7:7 to 28:7, the value of half time of crystallization (t_1/2) delayed form 2.85 to 5.31 min at 140°C. On the other hand, according to the Lauritzen–Hoffman theory, the fold‐surface energy (σ_e) was calculated. σ_e decreased from 77.7 to 73.3 erg/cm² with an increase in PLLA/PDLA block length ratio. Correspondingly increase in nucleation density was observed by the polarized optical microscope. Results indicated that the PLLA/PDLA block length ratio had a significant impact on the crystallization behavior of PPO–PDLA–PLLA copolymers. POLYM. ENG. SCI., 55:2534–2541, 2015. © 2015 Society of Plastics Engineers     

Increasing the compatibility of poly(l‐lactide)/poly(para‐dioxanone) blends through the addition of poly(para‐dioxanone‐co‐l‐lactide)

To modify the mechanical properties of a poly(l ‐lactide) (PLLA)/poly(para‐dioxanone) (PPDO) 85/15 blend, poly(para‐dioxanone‐co‐l ‐lactide) (PDOLLA) was used as a compatibilizer. The 85/15 PLLA/PPDO blends containing 1–5 wt % of the random copolymer PDOLLA were prepared by solution coprecipitation. Then, the thermal, morphological, and mechanical properties of the blends with different contents of PDOLLA were studied via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and tensile testing, respectively. The DSC result revealed that the addition of PDOLLA into the blends only slightly changed the thermal properties by inhibiting the crystallization degree of the poly(l ‐lactide) in the polymer blends. The SEM photos indicated that the addition of 3 wt % PDOLLA into the blend was ideal for making the interface between the PLLA and PPDO phases unclear. The tensile testing result demonstrated that the mechanical properties of the blends containing 3 wt % PDOLLA were much improved with a tensile strength of 48 MPa and a breaking elongation of 214%. Therefore, we concluded that the morphological and mechanical properties of the PLLA/PPDO 85/15 blends could be tailored by the addition of the PDOLLA as a compatibilizer and that the blend containing a proper content of PDOLLA had the potential to be used as a medical implant material. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41323.     

Micro‐ and nanostructures of polylactide stereocomplexes and their biomedical applications

The discovery of stereocomplexation, secondary interaction between enantiomeric poly(l ‐lactide) (PLLA) and poly(d ‐lactide) (PDLA) provides a method for the creation of novel biomaterials with distinctive chemical and physical stability. Stereocomplexation opens a new way for the preparation of diverse micro‐ and nanostructures such as uniform microspheres, hollow particles, micelles, nanocrystals, nanofibres, nanotubes and polymerosomes. Herein, we describe the design of stereocomplex assemblies for specific applications and methods for their preparation. This review focuses primarily on the use of stereocomplex assemblies in biomedical applications due to the improved stability and physicochemical properties in comparison to enantiomeric polylactides. To make the polylactide stereocomplexes soluble in water and, as a consequence, to improve compatibility with the human body, various amphiphilic copolymers with PLLA and PDLA enantiomeric segments can be prepared. Stereocomplexation can facilitate their self‐assembly into micro‐ and nanoparticles, stabilize the particle size and morphology and can also have an influence on the in vivo degradation rate and cytotoxicity of these materials. Stimuli‐responsiveness in stereocomplex assemblies can be achieved by copolymerization of lactide with, for example, thermoresponsive N‐isopropylacrylamide or amino acids with pH‐sensitive pendant groups. Stereocomplex micro‐ and nanoparticles are used for encapsulation of various bioactive compounds: anticancer drugs, antibiotics and proteins. Finally, examples of materials in which high thermal and mechanical stabilities delivered as a result of stereocomplexation play a crucial role, i.e. hydrogels, nanofibres, microcellular foams and artificial skin, are described. The preparation of biomaterials and biomedical systems based on polylactide stereocomplex assemblies opens new opportunities in this field. © 2015 Society of Chemical Industry     

Water vapor permeability of poly(lactide)s: Effects of molecular characteristics and crystallinity

Amorphous‐made poly(L ‐lactide) [i.e., poly(L ‐lactic acid) (PLLA)], poly(L ‐lactide‐co‐D ‐lactide)[P(LLA‐DLA)](77/23), and P(LLA‐DLA)(50/50) films and PLLA films with different crystallinity (X_c) values were prepared, and the effects of molecular weight, D ‐lactide unit content (tacticity and optical purity), and crystallinity of poly(lactide) [i.e., poly(lactic acid) (PLA)] on the water vapor permeability was investigated. The changes in number‐average molecular weight (M_n) of PLLA films in the range of 9 × 10⁴–5 × 10⁵ g mol^?1 and D ‐lactide unit content of PLA films in the range of 0–50% have insignificant effects on their water vapor transmission rate (WVTR). In contrast, the WVTR of PLLA films decreased monotonically with increasing X_c from 0 to 20%, while leveled off for X_c exceeding 30%. This is probably due to the higher resistance of “restricted” amorphous regions to water vapor permeation compared with that of the “free” amorphous regions. The free and restricted amorphous regions are major amorphous components of PLLA films for X_c ranges of 0–20% and exceeding 30%, respectively, resulting in the aforementioned dependence of WVTR on X_c. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Regulation of the mechanical properties and heat resistance of the poly(l‐lactide‐co‐trimethylene carbonate) copolymer by the incorporation of a stereocomplex crystal and graphene oxide

Stereocomplex crystals of polylactide and graphene oxide (GO) were simultaneously used to regulate the mechanical properties and heat resistance of a poly(l ‐lactide‐co‐trimethylene carbonate) [P(LLA‐co‐TMC)] copolymer. The crystallization behaviors in the nonisothermal cold‐crystallization process of P(LLA‐co‐TMC)–poly(d ‐lactide) (PDLA) blends and P(LLA‐co‐TMC)–PDLA–GO composites were investigated by differential scanning calorimetry, wide‐angle X‐ray diffraction, and polarized optical microscopy. Data from the crystallization kinetics and the crystallization active energy indicated that GO both promoted nucleation and limited growth during the stereocomplex crystallization process. Three kind of samples (without crystallization, with low crystallinity, and with high crystallinity) were used to investigate the mechanical properties and heat resistance. We found a decrease in the elongation at break when the stereocomplex crystal and GO contents were increased, and this was accompanied by an improvement in the tensile strength. The change in the storage modulus value determined by dynamic mechanical analysis demonstrated that both the stereocomplex crystal and GO effectively improved the heat resistance. These results indicate that this study provided a new strategy for fabricating a P(LLA‐co‐TMC) copolymer with good comprehensive properties at was entirely different from common chemical crosslinking methods. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45248.     

Surface modification of halloysite nanotubes with l‐lactic acid: An effective route to high‐performance poly(l‐lactide) composites

To improve the interfacial bonding between halloysite nanotubes (HNTs) and poly(l ‐lactide) (PLLA), a simple surface modification of HNTs with l ‐lactic acid via direct condensation polymerization has been developed. Two modified HNTs were obtained: HNTs grafting with l ‐lactic acid (l‐HNTs) and HNTs grafting with poly(l ‐lactide) (p‐HNTs). The structures and properties of l‐HNTs and p‐HNTs were investigated. Then, a series of HNTs/PLLA, l‐HNTs/PLLA and p‐HNTs/PLLA composites were prepared using a solution casting method and were characterized by polarized optical microscopy (POM), field scanning electron microscopy, and tensile testing. Results showed that l ‐lactic acid and PLLA could be easily grafted onto the surface of HNTs by forming an Al carboxylate bond and following with condensation polymerization, and the amounts of the l ‐lactic acid and PLLA grafted on the surface of the HNTs were 5.08 and 14.47%, respectively. The surface‐grafted l ‐lactic acid and PLLA played the important role in improving the interfacial bonding between the nanotubes and matrix. The l‐HNTs and p‐HNTs can disperse more uniformly in and show better compatibility with the PLLA matrix than untreated HNTs. As a result, the l‐HNTs/PLLA and p‐HNTs/PLLA composites had better tensile properties than that of the HNTs/PLLA composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41451.     

Effects of plasma treatment on biocompatibility of poly[(L‐lactide)‐co‐(ϵ‐caprolactone)] and poly[(L‐lactide)‐co‐glycolide] electrospun nanofibrous membranes

Poly[(l ‐lactide)‐co ‐(? ‐caprolactone)] (PLCL) and poly[(l ‐lactide)‐co ‐glycolide] (PLGA) copolymers are widely used in neural guide tissue regeneration. In this research, the surface modification of their hydrophilicity was achieved using plasma treatment. Attachment and proliferation of olfactory ensheathing cells on treated electrospun membranes increased by 26 and 32%, respectively, compared to the untreated PLCL and PLGA counterparts. Cells cultivated on both the PLCL and PLGA membranes showed high viability (>95%) and healthy morphologies with no evidence of cytotoxic effects. Cells grown on treated electrospun fibres displayed significant increases in mitochondrial activity and reductions in membrane leakage when compared to untreated samples. The results suggested that plasma treatment of the surface of the polymers enhanced both cell viability and growth without incurring any cytotoxic effects. © 2017 Society of Chemical Industry     

Macroporous hydrogels based on chitosan derivatives: Preparation,characterization, and in vitro evaluation

Chitosan‐based hydrogels are considered as promising biomaterials for tissue engineering. Biological properties of chitosan could be significantly improved by modification of its chemical structure. This study was aimed at characterizing macroporous hydrogels fabricated by freeze‐drying technique from chitosan, which has been N‐acetylated by 2,2‐bis(hydroxymethyl)propionic acid or l ,d ‐lactide. The nature of the acetylated agent was shown to significantly affect hydrogels morphology, swelling behavior, zeta‐potential, and protein sorption as well as their degradation by lysozyme. According to scanning electron and confocal laser scanning microscopy, the hydrogels possessed interconnected macroporous network that facilitated cells penetration into the interior regions of the hydrogel. Chemical modification of chitosan significantly influenced L929 cell growth behavior on hydrogel compared to the non‐modified chitosan. The proposed chemical strategy for modification of chitosan could be considered as promising approach for improvement of chitosan hydrogels. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44651.     

Effect of dimethyl sulfoxide on synthesis of thermoplastic cellulose‐Graft‐poly(l‐lactide) copolymer using ionic liquid as reaction media

In this study, ring‐opening graft polymerization of l ‐lactide onto cellulose was carried out homogeneously in ionic liquid (IL)/dimethyl sulfoxide (DMSO) co‐solvent as a reaction media. Through the effective control of high viscosity and steric hindrance caused by the interaction between the IL and the hydroxyl group of cellulose by adding DMSO as a co‐solvent, cellulose‐graft‐poly(l ‐lactide) (Cell‐g‐PLLA) copolymer with higher substitution efficiency was successfully prepared, at relatively low concentration of l ‐lactide. The maximum values of molar substitution, degree of lactyl substitution, and degree of polymerization of poly(l ‐lactide) in the copolymer were 3.76, 1.74, and 2.16, respectively, determined by ¹H‐NMR. The prepared cell‐g‐PLLA copolymers showed thermal plasticization with a glass transition temperature of 155°C. In addition, the thermal processibility could be improved as the amount of grafted PLLA in the copolymer increased. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41331.     

Enhanced toughness and strength of poly (d‐lactide) by stereocomplexation with 5‐arm poly (l‐lactide)

The enhancement of mechanical properties were achieved by solution blending of poly(d ‐lactide) (PDLA) and 5‐arm poly(l ‐lactide) (5‐arm PLLA). Differential scanning calorimetry (DSC) and wide‐angle X‐ray diffraction (WAXD) results indicated almost complete stereocomplex could be obtained when 5‐arm PLLA exceeded 30wt %. Tensile test results showed that the addition of 5‐arm PLLA in linear PDLA gave dramatically improvement both on tensile strength and elongation at break, which generally could not be increased simultaneously. Furthermore, this work transformed PDLA from brittle polymer into tough and flexible materials. The mechanism was proposed based on the TEM results: the stereocomplex crystallites formed during solvent evaporation on the blends were small enough (100–200 nm), which played the role of physical crosslinking points and increased the interaction strength between PDLA and 5‐arm PLLA molecules, giving the blends high tensile strength and elongation at break. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 132, 42857.     

Amino‐terminated polylactide micelles with an external poly(ethylene oxide) corona as carriers of drug‐loaded anionic liposomes

Micelles were prepared from a mixture of NH₂‐terminated poly(l ‐lactide) and poly(d ,l ‐lactide)‐block‐poly(ethylene oxide) (molar ratio of 3:7). The micelles were complexed with bilayer lipid vesicles (liposomes) composed of anionic palmitoyloleoylphosphatidylserine and zwitterionic dioleoylphosphatidylcholine in a molar ratio of 3:7. The micelles and micelle–liposome complexes were characterized using dynamic light scattering, laser electrophoresis, fluorimetry, transmission electron microscopy, enzymatic hydrolysis and cell viability with the following main findings. (i) Average diameter of micelle cores was found to be 70 ± 10 nm. (ii) Each micelle carried ca 20 000 amino groups. (iii) In a pH 7 solution the impact of the protonated NH₂ groups in the total surface of micelles was negligible owing to their screening by bulky poly(ethylene oxide) blocks. (iv) The micelles were stable in slightly acidic and neutral aqueous solutions, but aggregated in slightly alkaline solutions. (v) The micelles showed no cytotoxicity up to 0.04 mg mL^?1 concentration (the maximum concentration in the experiment). (vi) Each micelle adsorbed ca 30 anionic liposomes loaded with the antitumor antibiotic doxorubicin; the liposomes retained their integrity upon binding with micelles. (vii) The initial micelles and the micelle–liposome complexes showed two‐week stability to enzymatic hydrolysis. © 2018 Society of Chemical Industry     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.     

Novel thermosensitive hydrogel composites based on poly(d,l‐lactide‐co‐glycolide) nanoparticles embedded in poly(n‐isopropyl acrylamide) with sustained drug‐release behavior

To reach sustained drug release, a new composite drug‐delivery system consisting of poly(d,l ‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N‐isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free‐radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water‐in‐oil‐in‐water double‐emulsion solvent‐evaporation method. The release behavior of the composite hydrogels loaded with albumin–fluorescein isothiocyanate conjugate was studied and compared with that of the drug‐loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero‐order drug‐release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1°C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug‐release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40625.     

Influence of the synthesis conditions on the structural and thermal properties of poly(l‐lactide)‐b‐poly(ethylene glycol)‐b‐poly(l‐lactide)

The poly(l ‐lactide)‐b‐poly(ethylene glycol)‐b‐poly(l ‐lactide) block copolymers (PLLA‐b‐PEG‐b‐PLLA) were synthesized in a toluene solution by the ring‐opening polymerization of 3,6‐dimethyl‐1,4‐dioxan‐2,5‐dione (LLA) with PEG as a macroinitiator or by transterification from the homopolymers [polylactide and PEG]. Two polymerization conditions were adopted: method A, which used an equimolar catalyst/initiator molar ratio (1–5 wt %), and method B, which used a catalyst content commonly reported in the literature (<0.05 wt %). Method A was more efficient in producing copolymers with a higher yield and monomer conversion, whereas method B resulted in a mixture of the copolymer and homopolymers. The copolymers achieved high molar masses and even presenting similar global compositions, the molar mass distribution and thermal properties depends on the polymerization method. For instance, the suppression of the PEG block crystallization was more noticeable for copolymer A. An experimental design was used to qualify the influence of the catalyst and homopolymer amounts on the transreactions. The catalyst concentration was shown to be the most important factor. Therefore, the effectiveness of method A to produce copolymers was partly due to the transreactions. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40419.