Xuan Pang

Polylactic acid (PLA): Research, development and industrialization

Polylactide (PLA) is a biodegradable, aliphatic polyester derived from lactic acid. It has similar mechanical properties to polyethylene terephthalate, but has a significantly lower maximum continuous use temperature. PLA products can be recycled after use either by remelting and processing the material a second time or by hydrolyzing to lactic acid, the basic chemical. In this review, the technologies for polymerization of the lactic acid and the comparison of physical, thermal and mechanical properties, biodegradability, and biocompatibility of the PLA and copolymers with other similar polymers are described.

pH-Triggered Charge-Reversal Polypeptide Nanoparticles for Cisplatin Delivery: Preparation and In Vitro Evaluation

A series of pH-responsive random copolymer poly(l-glutamic acid-co-l-lysine) [P(Glu-co-Lys)] were synthesized through the ring-opening polymerization (ROP) of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) and 3-benzyloxycarbonyl-l-lysine N-carboxyanhydride (ZLys-NCA) and the subsequent deprotection. The chemical structure of the P(Glu-co-Lys)s was confirmed by NMR. Critical aggregation concentration and transmission electron microscopy measurements indicated that the P(Glu-co-Lys)s could self-assemble into aggregates in phosphate buffer. The surface charge of P(Glu-co-Lys) aggregates was greatly affected by the solutions pH and l-glutamic acid/l-lysine ratio because the carboxyl and amino groups present on the P(Glu-co-Lys) aggregates could be protonated or deprotonated to become charged. The pH value of the solution at which the surface charge of the P(Glu-co-Lys) aggregates reversed could be manipulated by the feed ratio of BLG-NCA and ZLys-NCA. In vitro methyl thiazolyl tetrazolium assays demonstrated that negatively charged P(Glu-co-Lys)s were nontoxic and biocompatible. Positive charged P(Glu-co-Lys)s showed some cytotoxicity to Hela cells. Cisplatin (CDDP) was used as a model anticancer drug to evaluate the charge-reversal drug delivery system. By the manipulation of CDDP loading content, the surface charge of the CDDP/P(Glu-co-Lys) nanoparticles could be reversed to positive from negative at tumor extracellular pH (pHe 6.5-7.2). An enhanced drug uptake and inhibition of cancer cell proliferation were observed for the tumoral pHe triggered charge-reversal CDDP/P(Glu-co-Lys) drug delivery system. These indicated that the CDDP/P(Glu-co-Lys) nanoparticles could be used as intelligent drug delivery systems for cancer therapy.

Enolic Schiff Base Aluminum Complexes and Their Catalytic Stereoselective Polymerization of Racemic Lactide

A series of enolic Schiff base aluminum(III) complexes LAlR (where L=NNOO-tetradentate enolic Schiff base ligand) containing ligands that differ in their steric and electronic properties were synthesized. Their single crystals showed that these complexes are five-coordinated around the aluminum center. Their coordination geometries are between square pyramidal and trigonal bipyramidal. Their catalytic properties in the solution polymerization of racemic lactide (rac-LA) were examined. The modifications in the auxiliary ligand exhibited a dramatic influence on the catalytic performance. Lengthening the backbone from C(2) alkylene to C(3) alkylene resulted in remarkable enhancement of both the stereoselectivity and the polymerization rate because of the increasing flexibility of the diimine backbone. Electron-withdrawing substituents in the diketone also highly improved the activity and the stereoselectivity. Among these complexes, 4 b had the highest activity and the stereoselectivity owing to the C(3) alkylene backbone and the two gem-methyl groups on the middle carbon atom. The value of the polymerization rate constant (k(p)) catalyzed by 4 b in 70 degrees C was 1.90 L mol(-1) min(-1), the activation energy of the polymerization (35.4 kJ mol(-1)) was calculated according to the Arrhenius equation. Other factors that influenced the polymerization, such as the polymerization time, the temperature, and the monomer concentration, are also discussed in detail.

Synthesis of Biodegradable and Electroactive Tetraaniline Grafted Poly(ester amide) Copolymers for Bone Tissue Engineering

Biodegradable poly(ester amide)s have recently been used as biomaterials due to their desirable chemical and biological characteristics as well as their mechanical properties, which are amendable for material processing. In this study, electroactive tetraaniline (TA) grafted poly(ester amide)s were successfully synthesized and characterized. The poly(ester amide)s-graft-tetraaniline copolymers (PEA-g-TA) exhibited good electroactivity, mechanical properties, and biodegradability. The biocompatibility of the PEA-g-TA copolymers in vitro was systematically studied, which demonstrated that they were nontoxic and led to favorable adhesion and proliferation of mouse preosteoblastic MC3T3-E1 cells. Moreover, the PEA-g-TA copolymers stimulated by pulsed electrical signal could serve to promote the differentiation of MC3T3-E1 cells compared with TCPs. Hence, the biodegradable and electroactive PEA-g-TA copolymers possessed the properties in favor of the long-time potential application in vivo (electrical stimulation directly to the desired area) as bone repair scaffold materials in tissue engineering.

Glucose-sensitive polypeptide micelles for self-regulated insulin release at physiological pH

Three novel phenylboronic acid functionalized block copolymers, monomethoxy poly(ethylene glycol)-b-poly(L-glutamic acid-co-N-3-L-glutamylamidophenylboronic acid) (mPEG-b-P(GA-co-GPBA)), were synthesized by modifying mPEG-b-PGA with 3-aminophenylboronic acid (APBA). The resultant diblock copolymers self-assembled into micelles in phosphate buffer at physiological pH (pH 7.4). More interestingly, at pH 7.4, the hydrodynamic radii (Rh) of the micelles increased with an increase in glucose concentration by formation of hydrophilic PBA–glucose complex. Thus, insulin, a model drug, was loaded into the glucose-sensitive polypeptide micelles. The in vitro release profiles revealed that the release of insulin from the micelles could be triggered by glucose, i.e. less insulin was released under healthy blood glucose level (1 mg mL−1 glucose), while quick release occurred under diabetic blood glucose level (above 2 mg mL−1 glucose). Furthermore, in vitro methyl thiazolyl tetrazolium (MTT) assays and hemolysis tests suggested that the copolymers had good biocompatibility. Therefore, the phenylboronic acid functionalized block copolymers with high glucose-sensitivity and good biocompatibility may have potential as self-regulated insulin release systems.

Bimetallic salen–aluminum complexes: synthesis, characterization and their reactivity with rac-lactide and ε-caprolactone

A series of bimetallic Schiff-base ligands were synthesized and used to prepare aluminum complexes. All the complexes were characterized by 1H, 13C NMR and elemental analysis. These complexes were used as catalysts in the rac-lactide and e-caprolactone polymerization. Isotactic enriched polylactides were obtained by using these complexes. All polymerizations were living with the narrow molar mass distributions. The Mn(obsd) of the isolated polymers was in good agreement with Mn(calcd). Kinetic studies showed that the polymerizations were first-ordered with respect to both lactide and caprolactone monomers. The more bulky substituents with more steric hindrance of the complexes had relatively poor activity. The increasing temperature had a positive effect as the polymerization rate increased with increasing temperature.

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.

Facile one-pot synthesis of glucose-sensitive nanogel via thiol-ene click chemistry for self-regulated drug delivery

A novel glucose-sensitive nanogel was conveniently prepared through one-pot thiol-ene copolymerization of pentaerythritol tetra(3-mercaptopropionate), poly(ethylene glycol) diacrylate, methoxyl poly(ethylene glycol) acrylate and N-acryloyl-3-aminophenylboronic acid. The formation of core-shell nanogel was verified by proton nuclear magnetic resonance, dynamic laser scattering (DLS) and transmission electron microscopy. The successful incorporation of phenylboronic acid (PBA) in the nanogel was confirmed through Fourier transform infrared spectroscopy, inductively coupled plasma mass spectrometry and fluorescence technology. Owing to the presence of PBA, the nanogel exhibited high glucose sensitivity in phosphate-buffered saline determined by DLS and fluorescence technology. The increased amount of glucose causes an increase in the hydrodrodynamic radius and a decrease in the fluorescence intensity of PBA-alizarin red S (ARS) complex in the nanogel at pH 7.4 because of the competitive substitution of ARS to form the hydrophilic PBA-glucose complex. ARS and insulin were loaded into this glucose-sensitive nanogel. In vitro release profiles revealed that the drug release from the nanogel could be triggered by the presence of glucose. The more glucose in the release medium, the more drug was released and the faster the release rate. Furthermore, in vitro methyl thiazolyl tetrazolium assay, lactate dehydrogenase assay and hemolysis test suggested that the nanogel was biocompatible. Therefore, the PBA-incorporated nanogel with high glucose-sensitivity and good biocompatibility may have great potential for self-regulated drug release.

Synthesis and characterization of half-salen complexes and their application in the polymerization of lactide and epsilon-caprolactone

A series of half-salen ligands and their aluminum Al(III) complexes that contained different substituents were designed and synthesized. All the ligands and their complexes were characterized by 1H, 13C NMR and elemental analysis. The complexes can be used as catalysts to produce polylactide and poly-e-caprolactone. All polymerizations were living with narrow molar mass distributions. The Mn(obsd) values of the isolated polymers were in good agreement with Mn(calcd). The polymerization rate of the electrophilic substituted complex was higher than the non-electrophilic substituted analogues. The more bulky substituents with more steric hindrance of the complexes showed relatively low polymerizing activity. The aluminum complexes showed a moderate stereo-selectivity to the ring opening polymerization of rac-lactide to give isotactic enriched polylactide.

Magnesium complexes bearing N,N-bidentate phenanthrene derivatives for the stereoselective ring-opening polymerization of rac-lactides

Three unreported magnesium complexes (1: R = C6H5, 2: R = 2,6-Et2C6H3, 3: R = 2-tBuC6H4) bearing N,N-bidentate phenanthrene derivatives derived from Schiff bases were synthesized. These complexes were characterized using 1H and 13C NMR spectroscopy and elemental analyses and employed for rac-lactide and L-lactide polymerization. Complex 1 showed the highest activity among these Mg complexes for the ring-opening polymerization (ROP) of L-lactide, and complex 3 showed the highest stereoselectivity for the ROP of rac-lactide, achieving partially heterotactic polylactide (PLA) with a Pr of 0.76. The polymerization kinetics utilizing 2 as a catalyst were researched in detail. The kinetics of the polymerization data revealed that the rate of polymerization was first-order with respect to monomer, and had an order of 0.97 with respect to catalyst. There was a linear relationship between the L-lactide conversion and the number-average molecular weight of PLA.