RESUMEN
AIMS: To investigate the effects of high doses of pentazocine on antinociception induced by a high dose of morphine and the role of the kappa-opioid receptors (KORs) in these effects in mice. MAIN METHODS: Sixty-six C57BL/6J mice were pretreated with a KOR antagonist, nor-binaltorphimine (nor-BNI) (10mg·kg(-1)), or a normal saline placebo. All the mice received a subcutaneous injection of morphine (10mg·kg(-1)) 120min later and different doses of pentazocine (3, 10, 30, 56, 100mg·kg(-1)) or a normal saline placebo. A tail pressure test, hot plate test and tail flick test were performed before and at 30, 60, 90 and 120min after the injection of morphine. KEY FINDINGS: The tail pressure test, hot plate test and tail flick test showed that pentazocine at doses of 10 to 100mg·kg(-1), but not at 3mg·kg(-1), had significant antagonizing effects on the antinociception induced by high-dose morphine to mechanical and thermal pain, and nor-BNI did not affect antinociception in combination with pentazocine at 10 to 100mg·kg(-1) and morphine at 10mg·kg(-1). SIGNIFICANCE: High-doses of pentazocine antagonize the antinociception induced by a high-dose of morphine in a dose-dependent manner, and this antagonistic effect is not associated with the activation of KORs.
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Analgésicos Opioides/farmacología , Morfina/farmacología , Dolor/tratamiento farmacológico , Pentazocina/farmacología , Receptores Opioides kappa/efectos de los fármacos , Analgésicos Opioides/administración & dosificación , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , Morfina/administración & dosificación , Naltrexona/análogos & derivados , Naltrexona/farmacología , Pentazocina/administración & dosificación , Receptores Opioides kappa/metabolismoRESUMEN
INTRODUCTION: The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac surgery. METHODS: RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints. RESULTS: Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery. CONCLUSION: Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos/métodos , Glicoproteínas/administración & dosificación , Forma MB de la Creatina-Quinasa/sangre , Cuidados Críticos , Mortalidad Hospitalaria , Humanos , Inflamación , Interleucina-6/sangre , Interleucina-8/sangre , Periodo Intraoperatorio , Tiempo de Internación , Elastasa de Leucocito/sangre , Oxígeno/química , Complicaciones Posoperatorias/prevención & control , Periodo Posoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Troponina I/sangre , Inhibidores de Tripsina/química , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: The aim of this study was to investigate the effects of ulinastatin, a protease inhibitor, and blood transfusion on perioperative surgical complications, changes of systemic inflammatory response syndrome (SIRS) scores, and levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) in patients undergoing liver resection. MATERIALS AND METHODS: Patients aged 18-65 years were enrolled and divided into four groups (12 patients in each group): a control group, a group given ulinastatin (UTI group), a group given blood transfusion (BT group), and a group given both blood transfusion and ulinastatin (BT+UTI group). Patients were randomised to receive ulinastatin or not, whereas blood transfusion was administered based on a transfusion trigger. Ulinastatin was given at a dose of 100,000 units/10 kg, infused 15 min before allogeneic blood transfusion or after completion of the liver resection. The patients were followed up for 3 days to record surgical complications, SIRS scores and levels of IL-6, IL-8 and TNF-α. RESULTS: Forty-four patients were included in the data analysis. The SIRS rate (SIRS scores≥2) was significantly higher in the BT groups than in the control group at 6 hours and on day 3 after surgery and was significantly lower in the BT+UTI group than in the BT group on day 3 after surgery. Allogeneic blood transfusion significantly increased and ulinastatin significantly decreased postoperative levels of IL-6, IL-8, and TNF-α. The length of stay in hospital was significantly longer in the BT groups than in the control group but was not significantly different between the BT+UTI and BT groups. CONCLUSION: A single dose of ulinastatin before allogeneic blood transfusion may lower the rate of postoperative SIRS and levels of IL-6, IL-8 and TNF-α associated with allogeneic blood transfusion and improve patients' postoperative recovery.
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Antiinflamatorios/uso terapéutico , Citocinas/sangre , Glicoproteínas/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Inhibidores de Proteasas/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Reacción a la Transfusión , Adolescente , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Coloides/administración & dosificación , Soluciones Cristaloides , Femenino , Estudios de Seguimiento , Glicoproteínas/administración & dosificación , Hepatectomía , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Soluciones Isotónicas/administración & dosificación , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Plasma , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Premedicación , Estudios Prospectivos , Inhibidores de Proteasas/administración & dosificación , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
AIM OF THE STUDY: Our previous studies indicated that processed Aconiti tuber (PAT), a traditional Chinese herbal medicine, had antinociceptive effects and inhibitory effects on morphine tolerance by activation of kappa-opioid receptor (KOR). Preclinical studies also demonstrated that KOR agonists functionally attenuate addictive behaviors of morphine, such as conditioned place preference (CPP). Therefore, we hypothesize that PAT may inhibit morphine-induced CPP in rats. MATERIALS AND METHODS: (1) Five groups of rats (n=8 for each group) were alternately subcutaneous (s.c.) injected with morphine 10mg/kg (one group receive normal saline as a control) and normal saline for 8 days and oral co-administrated with distilled water or PAT 0.3, 1.0, or 3.0 g/kg daily on days 2-9 during CPP training, respectively. (2) Other four groups of rats were randomly s.c. injected with nor-binaltorphimine (nor-BNI; 5mg/kg) or normal saline (as a control) 120 min before alternately s.c. with morphine and normal saline and oral co-administrated with distilled water or PAT 3.0 g/kg daily. Each rat was acquired pre-conditioning and post-conditioning CPP data and assayed dynorphin concentrations by radioimmunoassay in rat's nucleus accumbens (NAc) after CPP training. RESULTS: (1) PAT 1.0 or 3.0 g/kg dose-dependently decreased the morphine-induced increase of CPP scores. (2) Nor-BNI completely antagonized the inhibition of PAT on morphine-induced CPP. (3) PAT dose-dependently increased dynorphin content in rats' NAc after CPP training. CONCLUSIONS: (1) PAT dose-dependently inhibited morphine-induced CPP. (2) The inhibition of PAT on morphine-induced CPP was probably due to activation of KOR by increasing dynorphin release in rats' NAc.
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Aconitum , Conducta Adictiva/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Dependencia de Morfina/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Núcleo Accumbens/efectos de los fármacos , Fitoterapia , Animales , Conducta Adictiva/metabolismo , Conducta Animal/efectos de los fármacos , Condicionamiento Operante/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Medicamentos Herbarios Chinos/farmacología , Dinorfinas/metabolismo , Masculino , Naltrexona/análogos & derivados , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Núcleo Accumbens/metabolismo , Tubérculos de la Planta , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Opioides kappa/agonistasRESUMEN
New, biodegradable poly(L-lactide) disulfides, PLLA-SS-PLLA, were first prepared through the DMAP-catalyzed ring-opening polymerization of L-lactide with a dihydroxyethyl disulfide initiator, and were further catalytically reduced into thiol-end-functionalized poly(L-lactide)s, HO-PLLA-SH, with a tributyl phosphine catalyst (PBu3). Employing the HO-PLLA-SH as the ligand, new core-shell CdSe/PLLA quantum dots (QDs) were continuously prepared via a facile ligand-exchanging process with the CdSe/TOPO QD precursor. The chemical structures, morphologies and solvent solubility of these prepared CdSe/PLLA QDs were investigated by NMR spectroscopy, FTIR spectroscopy, XRD, TEM and excitation under either room light or UV radiation at 365 nm, demonstrating the successful ligand replacement and the new formation of core-shell CdSe/PLLA QDs (diameter:4.0 +/- 0.3 nm). Finally, UV and FL results indicate the two factors of the HO-PLLA-SH ligand molecular weight and the ligand/QD precursor feeding weight ratio were important for preparing stable and highly photoluminescent CdSe/PLLA QDs.
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Compuestos de Cadmio/síntesis química , Disulfuros/química , Disulfuros/síntesis química , Luminiscencia , Poliésteres/química , Poliésteres/síntesis química , Puntos Cuánticos , Compuestos de Selenio/síntesis química , Biodegradación Ambiental , Compuestos de Cadmio/química , Cromatografía en Gel , Espectroscopía de Resonancia Magnética , Microscopía Electrónica de Transmisión , Compuestos de Selenio/química , Solubilidad , Solventes/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Compuestos de Sulfhidrilo/química , Difracción de Rayos XRESUMEN
This study communicates the molecular design, preparation, and biological application of novel symmetric amphiphilic polycationic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D2-LLA15-D2 bearing two two-generation poly(L-lysine) PLL dendrons D2 and a central hydrophobic biodegradable poly(L-lactide) block LLA15. First, an amino-protected precursor of L1-OH was designed and synthesized and was further employed to prepare L1-LLA15 with an organic 4-(dimethylamino)-pyridine-mediated living-ring-opening polymerization of l-lactide. Subsequently, the hydroxy end-capped L1-LLA15 was coupled to synthesize a new triblock L1-LLA15-L1 with two one-generation amino-protected PLL dendrons L1. Furthermore, with a repeated trifluoroacetic-acid-mediated amino deprotection-protection cycle, new amphiphilic triblock D2-LLA15-D2 was successfully prepared. By means of NMR, mass spectrometry, and gel permeation chromatography, these synthetic precursors and final amphiphilic product were characterized to bear well-defined triblock structures. In addition, this synthesized amphiphilic triblock polycationic macromolecule was applied as a new polycationic plasmid DNA carrier, and its DNA binding affinity was examined via an agarose electrophoresis and a fluorescence titration assay along with two important references of hydrophilic dendritic D2-HEX-D2 and double-hydrophilic D2-PEG-4K-D2 bearing the same two D2 dendrons; much enhanced DNA binding affinity was interestingly revealed for the new amphiphilic structural D2-LLA15-D2. Moreover, the assembled polyplex microparticles of plasmid DNA/polycationic carrier were further analyzed by dynamic light scattering and transmission electron microscopy, indicating their averaged nanoparticle size around 150-200 nm. As for the cytotoxicity of the new D2-LLA15-D2, MTT assays were conducted with a human hepatocellular carcinoma cell line (SMMC-7721), indicating a very low cytotoxicity as compared with commercial linear PLL-23K and PEI-2K, and a DNase I degradation of the assembled polyplex particles was also done in the HBS buffer solution to evaluate their stabilities. Finally, employing the new amphiphilic D2-LLA15-D2 as gene carrier, in vitro gene transfection experiments were conducted with the SMMC-7721 cell line, indicating a transfection efficiency increase of at least 10 times higher than that of the naked plasmid DNA under a N/P charge ratio of 10. Therefore, these interesting results may provide a new possible way to construct efficient polycationic macromolecular gene carriers with low toxicity and less expensive low-generation PLL dendrons.
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ADN/química , Técnicas de Transferencia de Gen , Plásmidos/química , Poliésteres/química , Polilisina/análogos & derivados , Dendrímeros/química , Poliésteres/síntesis química , Polilisina/síntesis química , Polilisina/químicaRESUMEN
This study presents new investigations on chemical syntheses and characterization of new asymmetric AB(n)-shaped amphiphilic diblock methoxy poly(ethylene glycol)-b-[poly(l-lactide)](n), MPEG-b-(PLLA)(n) (n = 2, 4, and 8), bridged with dendritic ester linkages. First, a new series of A(OH)(n)-shaped hydroxy end-capped MPEG-(OH)(2), MPEG-(OH)(4), and MPEG-(OH)(8) bearing corresponding one- to three-generation dendritic ester moieties were efficiently derived from the starting MPEG (M(n) = 2 KDa) and 2,2'-bis(hydroxymethyl)propionic acid (Bis-HMPA) via ester coupling and a facile hydroxy protection-deprotection cycle, and then, chemical structures of these functional MPEG-(OH)(n) were characterized by nuclear magnetic resonance spectrometry (NMR) and MALDI-FTMS. Subsequently, by employing these MPEG-(OH)(n) as functional macroinitiators, new asymmetric AB(n)()-shaped amphiphilic MPEG-b-(PLLA)(2) S1, MPEG-b-(PLLA)(4) S2, and MPEG-b-(PLLA)(8) S3 bridged with dendritic Bis-HMPA ester linkages of L1-L3 as well as linear structural MPEG-b-PLLA references (R1-R3) were synthesized through the SnOct(2)-catalyzed ring-opening polymerization (ROP) of l-lactide at 130 degrees C in m-xylene solution, and their structures were further examined by NMR and gel permeation chromatography (GPC). It was demonstrated that the functional MPEG-(OH)(n) efficiently initiated the ROP of LLA, finally leading to successful formation of the AB(n)-shaped amphiphilic MPEG-b-(PLLA)(n) (n = 2, 4, and 8) with each PLLA arm weight close to 2 KDa and very narrow molecular weight distribution. Moreover, thermal history, crystallization, and spherulite morphologies were studied by means of differential scanning calorimeter (DSC), thermal gravimetric analyzer (TGA), and polarized microscope (POM) for these new structural amphiphilic S1-S3 as well as the linear R1-R3, intriguingly indicating a strong molecular architecture dependence of segmental crystallizability, spherulite morphology, and apparent crystal growth rate. Due to the favorable biodegradability and biocompatibility of the PLLA and MPEG, these results may therefore create new possibilities for these novel structural AB(n)-shaped amphiphilic MPEG-b-(PLLA)(n) as potential biomaterials.
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Dendrímeros/síntesis química , Lactatos/síntesis química , Polietilenglicoles/síntesis química , Reactivos de Enlaces Cruzados/química , Dendrímeros/química , Ésteres/química , Hidroxiácidos , Lactatos/química , Espectroscopía de Resonancia Magnética , Polietilenglicoles/química , Propionatos/químicaRESUMEN
This study presents investigations on new approaches to novel biodegradable amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s bearing well-defined structures. First, two new Boc-protected poly(L-lysine) dendron initiators G(2)OH 4 (generation = 2) and G(3)OH 6 (generation = 3) with hydroxyl end functional groups were efficiently derived from corresponding precursors 3 and 5 via methyl ester substitution with ethanolamine. Subsequently, two series of new diblock copolymers of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s (S1-S2, S3-S4) were prepared in chloroform through ring-opening copolymerization of poly(L-lactide)s with a metal-free catalyst of organic 4-(dimethylamino) pyridine (DMAP) in the presence of a corresponding new poly(L-lysine) dendron initiator. Further, molecular structures of the prepared new dendron initiators as well as those of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s bearing different dendron blocks and PLLA lengths were examined by means of nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), mass spectrometry (ESI-MS, MALDI-FTMS), and thermal gravimetric analysis (TGA). The results demonstrated successful formation of the synthetic precursors, functional dendron initiators, and new diblock copolymers. In addition, the very narrow molecular weight distributions (PDI = 1.10-1.14) of these poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s further indicated their well-defined molecular structures. After the efficient Boc-deprotection for the dendron amino groups with TFA/CH(2)Cl(2), new diblock poly(L-lactide)-b-dendritic poly(L-lysine)s bearing lipophilic PLLA and hydrophilic dendritic PLL were finally prepared. It was noteworthy that the MALDI-FTMS result showed that no appreciable intermolecular chain transesterification happened during the ROP of L-lactide catalyzed by the DMAP. Moreover, self-assembly of these new biodegradable amphiphilic copolymers in diverse solvents were also preliminarily studied.
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Antracenos/química , Dendrímeros/síntesis química , Tensoactivos/síntesis química , Catálisis , Dendrímeros/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Metales/química , Estructura Molecular , Poliésteres/síntesis química , Poliésteres/química , Proteínas/síntesis química , Proteínas/química , Tensoactivos/química , TemperaturaAsunto(s)
Fumaratos/química , Polienos/química , Poliésteres/química , Agua/química , Materiales Biocompatibles , Biodegradación Ambiental , Carbono/química , Cromatografía de Gases , Calor , Radical Hidroxilo , Sustancias Macromoleculares/química , Espectroscopía de Resonancia Magnética , Modelos Químicos , Solubilidad , Solventes , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Factores de Tiempo , Difracción de Rayos XRESUMEN
In our previous study [J. Yang, L. Jia, L. Yin, J. Yu, Z. Shi, Q. Fang, A. Cao, Macromol. Biosci. 2004, 4, 1092.], new biodegradable copolymers of diblock methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) and methoxy poly(ethylene glycol)-block-poly(delta-valerolactone), and triblock poly(epsilon-caprolactone)-block-poly(ethylene glycol)-block-poly(epsilon-caprolactone) and poly(delta-valerolactone)-block-poly(ethylene glycol)-block-poly(delta-valero-lactone) bearing narrow molecular weight distributions and well-defined block architectures were reported to be prepared with our original aluminum metal complex templates. This work will continue to report new investigations on their water solubility, and reversible thermal responsive micellization and solution to gel transition in distilled water. Among the new synthesized copolymers (P1-P23), seven diblock or triblock samples (P3, P6, P7, P11, P12, P19, and P21) with higher hydrophilic building block populations were revealed to be water soluble under ambient temperature. By means of UV spectrophotometer attached with a thermostat, important parameters as critical micellization mass concentrations (CMCs) and critical micellization temperatures (CMTs) were characterized for these new amphiphile dilute aqueous solution with the aid of an lipophilic organic dye probe of 1,6-diphenyl-1,3,5-hexatriene (DPH). Furthermore, the critical gelation temperatures (CGTs) were simultaneously investigated for these water-soluble block copolymers via a tube tilting method. It was found that the CMC, CMT, and CGT were strongly affected by the population and nature of the hydrophobic building blocks, and a higher hydrophobicity of the new amphiphilic block copolymer finally led to lower CMC and CMT, and higher CGT. In addition, the salts of KBr and NaCl were found to play as a salt-out effect on the solution to gel transition for the diblock P6 and triblock P11, exhibiting an interesting tunable gelation temperature close to 35-42 degrees C. These results will pave new possibility for the synthesized block structural amphiphiles as potential biomaterials to be applied in vivo.
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Transición de Fase , Poliésteres/química , Polímeros/química , Pironas/química , Tensoactivos/química , Compuestos de Alumbre/química , Bromuros/química , Catálisis , Difenilhexatrieno/química , Micelas , Polietilenglicoles/química , Compuestos de Potasio/química , Cloruro de Sodio/química , Solubilidad , Espectrofotometría Ultravioleta , Temperatura de Transición , Agua/químicaRESUMEN
This study presents syntheses, structural characterization, and crystallization kinetic investigation of new structurally well-defined star-shaped poly(l-lactide)s (PLLAs). First, a series of new 3- to 6-arm star-shaped PLLAs were synthesized through SnOct(2) catalyzed ring-opening polymerization of (l)-lactide with natural sugar alcohols of glycerol, erythritol, xylitol, and sorbitol as the favorable initiators. Subsequently, their chemical structures were characterized by means of GPC, NMR, and viscometer with respect to the star-shaped structures, demonstrating the well-defined arm structures as evidenced on the g(1/2)/g' values, where g and g' denote the ratios of mean-square radius of gyration and intrinsic viscosity of a star-shaped polymer to those of a linear structural reference with similar absolute molecular weight. Furthermore, spherulite morphologies and growth rates were studied by a polarized microscopy (POM) for the synthesized star-shaped PLLAs with different molecular weights, and it was found that the more arms of a star-shaped PLLA finally resulted in a lower spherulite growth rate. With regard to the crystallization kinetics of these star-shaped PLLAs, isothermal and nonisothermal crystallization were examined by differential scanning calorimeter (DSC). It was found that Avrami exponent n values of isothermal crystallization were almost independent of the isothermal crystallization temperature T(c) for different series of star-shaped PLLAs. In contrast, the values of Avrami exponent n were observed to strongly depend on the star-shaped structures with different arms, implying their distinct nucleation mechanisms, and the more arms of a star-shaped PLLA led to a slower isothermal crystallization rate. On the basis of a modified Avrami equation, new light was shed on the nonisothermal crystallization kinetics for the star-shaped PLLAs, and the activation energies were found to vary from 146.86 kJ/mol for the linear PLLA EG-3 to 221.23 kJ/mol of the star-shaped S-3, demonstrating much decreased crystallizabilities of star-shaped PLLAs with more arms.
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Poliésteres/química , Alcoholes del Azúcar/química , Biodegradación Ambiental , Cromatografía en Gel , Cristalización , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , ViscosidadRESUMEN
In situ self-assemblies of new biodegradable triblock PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA have been investigated in acetonitrile solution. At first, two series of PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA, respectively denoted as the P and Q triblock copolyester series, were prepared with fixed PBS block ((overline) M(n,NMR) = 6.9 kDa) and diverse enantiomeric PLLA/PDLA blocks. Further, their chemical structures and thermal properties were characterized by means of titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), polarimeter, wide-angle X-ray diffraction (WAXD) and thermal analytical instruments. When mixing the synthesized enantiomeric copolyester pairs denoted as P(1)/Q(1) - P(8)/Q(8) in acetonitrile solution at 60 degrees C, in situ self-assemblies were found to happen for the P(4)/Q(4) to P(8)/Q(8) pairs, bearing longer enantiomeric PLA block lengths. DSC and WAXD analysis of the self-assembled microparticles demonstrated that PLLA/PDLA racemic crystals were formed for the P(5)/Q(5) - P(8)/Q(8) systems, as evidenced by their melting points over 200 degrees C, and a new X-ray diffraction peak detected at 2theta = 11.8 degrees . Moreover, morphological studies by scanning electron microscopy (SEM) indicated the formation of disk- or platelet-like microparticles. It was noted that the diameters of the microparticles self-assembled in situ decreased from 1.28-1.50 mum down to 480-660 nm, through tailoring the enantiomeric PLA block length. Other factors, such as a central PBS block, the enantiomeric block length and the preparation conditions were suggested to play important roles in the in situ self-assembly of these enantiomeric triblock copolyesters. These results provide a facile way to self-assemble hydrophobic, biodegradable microparticles, through tuning the important van der Waals stereocomplexation interactions between two enantiomeric blocks in solution.
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Polienos , Poliésteres , Polímeros/síntesis química , Succinatos , Acetonitrilos , Biodegradación Ambiental , Cristalografía por Rayos X , Calor , Espectroscopía de Resonancia Magnética , Microscopía Electrónica de Rastreo , Polímeros/química , SolventesRESUMEN
In a previous study, we have reported chemical synthesis of novel aliphatic poly(butylene succinate-co-cyclic carbonate) P(BS-co-CC)s bearing various functionalizable carbonate building blocks, and this work will continue to present our new studies on their enzymatic degradation and in vitro cell biocompatibility assay. First, enzymatic degradation of the novel P(BS-co-CC) film samples was investigated with two enzymes of lipase B Candida Antartic (Novozyme 435) and lipase Porcine Pancreas PPL, and it was revealed that copolymerizing linear poly(butylene succinate) PBS with a functionalizable carbonate building block could remarkably accelerate the enzymatic degradation of a synthesized product P(BS-co-CC), and its biodegradation behavior was found to strongly depend on the overall impacts of several important factors as the cyclic carbonate (CC) comonomer structure and molar content, molar mass, thermal characteristics, morphology, the enzyme-substrate specificity, and so forth. Further, the biodegraded residual film samples and water-soluble enzymatic degradation products were allowed to be analyzed by means of proton nuclear magnetic resonance (1H NMR), gel permeation chromatograph (GPC), differential scanning calorimeter (DSC), attenuated total reflection FTIR (ATR-FTIR), scanning electron microscope (SEM), and liquid chromatograph-mass spectrometry (LC-MS). On the experimental evidences, an exo-type mechanism of enzymatic chain hydrolysis preferentially occurring in the noncrystalline domains was suggested for the synthesized new P(BS-co-CC) film samples. With regard to their cell biocompatibilities, an assay with NIH 3T3 mouse fibroblast cell was conducted using the novel synthesized P(BS-co-CC) films as substrates with respect to the cell adhesion and proliferation, and these new biodegradable P(BS-co-CC) samples were found to exhibit as low cell toxicity as the PLLA control, particularly the two samples of poly(butylene succinate-co-18.7 mol % dimethyl trimethylene carbonate) P(BS-co-18.7 mol % DMTMC) and poly(butylene succinate-co-21.9 mol % 5-benzyloxy trimethylene carbonate) P(BS-co-21.9 mol % BTMC) were interestingly found to show much better cell biocompatibilities than the PLLA reference.