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Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.
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With the escalation of plastic bans and restrictions, bio-based plastics, represented by polylactic acid (PLA), have become a major alternative to traditional plastics in the current market and are unanimously regarded as having potential for development. However, there are still several misconceptions about bio-based plastics, whose complete degradation requires specific composting conditions. Bio-based plastics might be slow to degrade when it is released into the natural environment. They might also be harmful to humans, biodiversity and ecosystem function as traditional petroleum-based plastics do. In recent years, with the increasing production capacity and market size of PLA plastics in China, there is an urgent need to investigate and further strengthen the management of the life cycle of PLA and other bio-based plastics. In particular, the in-situ biodegradability and recycling of hard-to-recycle bio-based plastics in the ecological environment should be focused. This review introduces the characteristics, synthesis and commercialization of PLA plastics, summarizes the current research progress of microbial and enzymatic degradation of PLA plastics, and discusses their biodegradation mechanisms. Moreover, two bio-disposal methods against PLA plastic waste, including microbial in-situ treatment and enzymatic closed-loop recycling, are proposed. At last, the prospects and trends for the development of PLA plastics are presented.
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Humans , Ecosystem , Biodegradable Plastics , Polyesters , Biodegradation, EnvironmentalABSTRACT
Resumen En términos generales, es bien conocida la cualidad que poseen algunos polímeros de cambiar sus propiedades físicas y químicas finales mediante la adición de nanopartículas a la matriz polimérica para producir un material compuesto (MC). Esta investigación está basada en la obtención de un MC a partir de ácido poliláctico (PLA) y nanotubos de carbono de pared múltiple (NTCPM), muy empleado en la industria del envasado y dispositivos biomédicos, con el fin de ampliar su perfil industrial. Se desarrollaron cuatro mezclas de PLA y NTCPM, y se empleó polietilenglicol (PEG) como plastificante. Se evaluaron sus propiedades morfológicas, térmicas, mecánicas, termo-mecánicas, espectroscópicas, ángulo de contacto y cristalográficas. Se observó que los MCs presentaron degradación térmica a temperaturas inferiores a la matriz sin NTCPM, así como un aumento en el módulo de flexión y tensión en algunas de las muestras. Así mismo, se observó que los NTCPM pueden aumentar la cristalinidad del material y que, en algunos casos, se incrementa su rigidez, actuando como un aditivo útil para aplicaciones de mayor esfuerzo mecánico que la matriz. Del efecto de agregar PEG en los MC, se determinó que los NTCPM no restringen la movilidad de las cadenas poliméricas y se da un efecto plastificante, lo que permite mayor movilidad de la zona amorfa de las cadenas de polímero, como indica la literatura consultada. Finalmente, se concluyó que a mayores contenidos de NTCPM, se generan mejores valores en el módulo de flexión, esfuerzo máximo de flexión, módulo de elongación, esfuerzo de carga máxima y esfuerzo de ruptura, entre otras propiedades evaluadas.
Abstract The quality of some polymers to change their final physical and chemical properties by adding nanoparticles to the polymer matrix to produce a composite material (MC) is well known. This research is based on obtaining a MC from polylactic acid (PLA) and multi-walled carbon nanotubes (CNTMW), widely used in the packaging industry and biomedical devices, in order to expand its industrial profile. Four mixtures of PLA and CNTMW were developed, and polyethylene glycol (PEG) was used as a plasticizer. Their morphological, thermal, mechanical, thermo-mechanical, spectroscopic, contact angle, and crystallographic properties were evaluated. It was observed that the composites showed thermal degradation at temperatures below the matrix without CNTMW, as well as an increase in the modulus of flexion and tension in some of the samples. Likewise, it was observed that the CNTMW can increase the crystallinity of the material and that, in some cases, its rigidity is increased, acting as a useful additive for applications of greater mechanical stress than the matrix. From the effect of adding PEG in the composites, the CNTMW do not restrict the mobility of the polymer chains and a plasticizing effect occurs, which allows greater mobility of the amorphous zone of the polymer chains. In general terms, it was concluded that at higher CNTMW contents, better values were generated in the flexural modulus, maximum flexural stress, elongation modulus, maximum load stress and rupture stress, among other evaluated properties.
Resumo Alguns polímeros têm a propriedade de alterar suas propriedades físicas e químicas finais, adicionando nanopartículas à matriz polimérica para produzir um composto. Esta pesquisa baseia-se na obtenção de composto partir de ácido polilático (PLA) e nanotubos de carbono de paredes múltiplas (MWCNT), amplamente utilizado na indústria de embalagens e dispositivos biomédicos, a fim de expandir seu perfil industrial. Foram desenvolvidas quatro misturas de PLA e MWCNT e o polietilenoglicol (PEG) foi usado como plastificante. Foram avaliadas suas propriedades morfológicas, térmicas, mecânicas, termo-mecânicas, espectroscópicas, ângulo de contato e cristalográficas. Observou-se que os compostos apresentaram degradação térmica em temperaturas abaixo da matriz sem MWCNT, além de aumento no módulo de flexão e tensão em algumas das amostras. Da mesma forma, observou-se que o MWCNT pode aumentar a cristalinidade do material e que, em alguns casos, sua rigidez é aumentada, atuando como um aditivo útil para aplicações de maior tensão mecânica que a matriz. A partir do efeito da adição de PEG nos compostos, determinou-se que o MWCNT não restringe a mobilidade das cadeias poliméricas e ocorre um efeito plastificante, que permite maior mobilidade da zona amorfa das cadeias poliméricas. Em termos gerais, concluiu-se que, com maiores teores de MWCNT, melhores valores foram gerados no módulo de flexão, tensão máxima de flexão, módulo de alongamento, tensão de carga máxima e tensão de ruptura, entre outras propriedades avaliadas.
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After entering the physiological environment, proteins and other biomolecules bind to the nanoparticles' surface, called protein corona. The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors. Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona. With folic acid (FA)-modified polylactic acid-polyglycolic acid copolymer (PLGA) nanoparticles, the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma. All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee (2019-409-1). Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed. The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct, particularly for proteins with molecular weight of 45, 110 and >180 kDa. Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells. Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization. The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions. Additionally, the protein corona in different diseases is emerging as a key point; thus, a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.
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To prepare the mimetic exosomes and co-delivery proteins and nucleic acids, and achieve efficient and safe co-delivery of multi-component drugs, an optimized formulation was designed by modifying a polylactic acid-glycolic acid copolymer (PLGA) matrix with a cationic lipid excipient dioleyl trimethylammonium propane (DOTAP), and a PLGA/DOTAP nanoparticles packaged protein and nucleic acid was prepared by double emulsion method, and the outermost membrane structure prepared by reverse phase evaporation method and consists of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol and membrane proteins. The structure of the mimetic exosomes is formed by ultrasonic dispersion and extrusion, and analyzed its characteristics and nature of the transfer effect. The size of mimetic exosomes was about 156.13 nm, with negative charge (-18.23 ± 0.57 mV), and it could efficiently co-transfer protein and siRNA, and siRNA could effectively inhibit the expression of target gene Trim28. The mimetic exosomes simulate the structure of exosomes and achieve safe and efficient co-delivery of multi-component drugs.
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BACKGROUND: The three-dimensional organic/inorganic scaffold materials using polymer/bioceramic composites can endow the necessary physical and chemical properties and enhance the mechanical properties of the materials. However, most bone substitution materials cannot prevent infection at the defect site. It has been found that the degradation of magnesium can produce local alkaline environment, so that magnesium has certain antibacterial activity. OBJECTIVE: To investigate the in vitro antibacterial activity and cytocompatibility of magnesium-containing scaffolds. METHODS: Polylactic acid/β-tricalcium phosphate/magnesium porous scaffolds were prepared by low-temperature rapid prototyping technology. The PTM (2:1) and PTM (1:2) groups referred to two mixing mass ratios (β-tricalcium phosphate:magnesium = 2:1 and 1:2), respectively. Two scaffolds of polylactic acid (P group) and polylactic acid/β-tricalcium phosphate (PT group) were also prepared by low-temperature rapid prototyping technology. The surface morphology, pore size, porosity and compression modulus of the scaffolds were measured. Staphylococcus aureus (ATCC 35923) was seeded on the scaffolds of each group for 24 hours. The antibacterial activity of the scaffolds was observed through spread plate method and confocal laser scanning microscopy. Mouse preosteoblasts MC3T3-E1 were co-cultured with the scaffolds of each group. The cell attachment and proliferation were evaluated by cell counting kit-8 assay. RESULTS AND CONCLUSION: (1) A relatively uniform porous structure was found on the scaffold surfaces in each group. There were no significant differences in the pore size and porosity among groups (P > 0.05). (2) The compression modulus in the PTM (2:1) and PTM (1:2) groups were significantly higher than those in the P and PT groups (P 0.05). (4) After 6 hours of culture, the number of attached cells in the PT, PTM (2:1) and PTM (1:2) groups was greater than that in the P group (P 0.05). (5) At 1 day of culture, the cell proliferation in the PT group was superior to that in the P group (P 0.05). (6) These results indicate that the polylactic acid/β-tricalcium phosphate/magnesium scaffold not only possesses good antibacterial activity, but also exhibits excellent cytocompatibility and certain anti-compressive ability.
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BACKGROUND: The dense microstructure of biological scaffolds and the limitation of cell growth microenvironment are the two major difficulties in the application of biological scaffolds in bone tissue repair. OBJECTIVE: To prepare fluffy hydroxyapatite/polylactic acid composite fiber scaffold, so that cells can easily enter into the scaffold and to realize three-dimensional culture of bone marrow mesenchymal stem cells. METHODS: Fluffy hydroxyapatite/polylactic acid composite scaffold was prepared by using modified electrospinning technology combined with biomineralization. The physical and chemical properties of the fiber scaffold were measured and observed. Human bone marrow mesenchymal stem cells were inoculated on the fluffy hydroxyapatite/polylactic acid composite scaffold and traditional hydroxyapatite/polylactic acid composite scaffold. Cell proliferation, adherence and morphological changes were detected. RESULTS AND CONCLUSION: (1) The thickness of hydroxyapatite coating in the fluffy hydroxyapatite/polylactic acid composite scaffold was about 8.3 µm, most of hydroxyapatite fibers were in discrete state with a diameter of 8-14 µm. The fibers were connected by pores, and the pore diameter was (65±35) µm. The surface area, porosity and water absorption of the scaffold were significantly higher than those of the traditional scaffold (P < 0.01). (2) After 12 hours of culture, the adherence of bone marrow mesenchymal stem cells on the two scaffolds was similar, 83% and 81% cells adhered on the traditional and fluffy scaffolds, respectively. (3) After 7 days of culture, the number of proliferated cells in the fluffy hydroxyapatite/polylactic acid composite scaffold was significantly more than that in the traditional hydroxyapatite/polylactic acid composite scaffold (P < 0.01). (4) After 7 days of culture, FDA staining and scanning electric microscopy showed that cell-cell independent shape appeared in the traditional scaffold. A large number of cells appeared in the fluffy scaffold and grew into cell clusters with high cell activity, which formed a cell-fiber construction. These results indicate that this new type hydroxyapatite/polylactic acid composite scaffold is beneficial for cell entry and proliferation.
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BACKGROUND: Transforming growth factor Β3/polylactic acid-glycolic acid (TGF-Β3/PLGA) sustained-release microspheres can maintain the effective drug concentration at the site of action and provide the feasibility for efficient utilization of growth factors. OBJECTIVE: To optimize the manufacturing process of TGF-Β3/PLGA sustained-release microspheres, and investigate their effects on the proliferation and migration of rabbit adipose-derived mesenchymal stem cells (ADSCs). METHODS: TGF-Β3/PLGA sustained-release microspheres were prepared by emulsification-solvent evaporation method. The morphology, particle size, drug spatial distribution, encapsulation efficiency, drug loading, and sustained release properties of the microspheres were characterized. The TGF-Β3/PLGA sustained-release microspheres were dissolved in phosphate buffered saline. The concentration of TGF-Β3 in the supernatant was detected at the corresponding time points. The microsphere morphology was observed by scanning electron microscopy at the corresponding time point. Adipose-derived mesenchymal stem cells were divided into six groups and then cultured with single culture medium (negative control) or culture medium containing TGF-Β3 or blank PLGA, or culture medium containing 10,100,1 000 g/L TGF-Β3/PLGA microspheres. Cell proliferation was detected by CCK-8 assay at the corresponding time point. Cells in each group were cultured for 24 hours with corresponding medium in a non-contact manner. The number of migratory cells was counted. RESULTS AND CONCLUSION: (1) TGF-Β3/PLGA sustained-release microspheres were spherical with smooth surface, no adhesion, and evenly distributed particle size. The microspheres had a diameter of 2-50 µm, and the protein drugs in the microspheres were evenly distributed, with high encapsulation efficacy and encapsulation dose. (2) The TGF-Β3/PLGA sustained-release microspheres had good degradation properties and were completely degraded after 6 months in vitro. At the same time, these microspheres had good sustained-release performance and released TGF-Β3 slowly for 45 days in vitro. (3) Blank microspheres and the sustained-release microspheres containing TGF-Β3 had no effect on the proliferation of adipose-derived mesenchymal stem cells. (4) Blank microspheres had no effect on the migration of adipose-derived mesenchymal stem cells, and the transforming growth factor 3 and the sustained-release microspheres containing TGF-Β3 promoted the migration of adipose-derived mesenchymal stem cells. There was no significant difference in the migration promotion between different concentrations of TGF-Β3. (5) These findings suggest that the TGF-Β3/PLGA sustained-release microspheres can promote the migration of adipose-derived mesenchymal stem cells without affecting their proliferation.
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Polyhydroxyalkanoate (PHA) is a representative biodegradable polymer with more than 150 varieties and various properties. This article reviews the research status and potential applications of PHA, and introduces the properties of four-generation commercial PHA and its research progress in blend fibers with other biodegradable materials.
Subject(s)
Biodegradable Plastics , Chemistry , Reference Standards , Materials Science , Polyhydroxyalkanoates , ChemistryABSTRACT
BACKGROUND: The dense microstructure of biological scaffolds and the limitation of cell growth microenvironment are the two major difficulties in the application of biological scaffolds in bone tissue repair. OBJECTIVE: To prepare fluffy hydroxyapatite/polylactic acid composite fiber scaffold, so that cells can easily enter into the scaffold and to realize three-dimensional culture of bone marrow mesenchymal stem cells. METHODS: Fluffy hydroxyapatite/polylactic acid composite scaffold was prepared by using modified electrospinning technology combined with biomineralization. The physical and chemical properties of the fiber scaffold were measured and observed. Human bone marrow mesenchymal stem cells were inoculated on the fluffy hydroxyapatite/polylactic acid composite scaffold and traditional hydroxyapatite/polylactic acid composite scaffold. Cell proliferation, adherence and morphological changes were detected. RESULTS AND CONCLUSION: (1) The thickness of hydroxyapatite coating in the fluffy hydroxyapatite/polylactic acid composite scaffold was about 8.3μ m, most of hydroxyapatite fibers were in discrete state with a diameter of 8-14μm. The fibers were connected by pores, and the pore diameter was (65±35) μm. The surface area, porosity and water absorption of the scaffold were significantly higher than those of the traditional scaffold (P<0.01).(2) After 12 hours of culture, the adherence of bone marrow mesenchymal stem cells on the two scaffolds was similar, 83% and 81% cells adhered on the traditional and fluffy scaffolds, respectively. (3) After 7 days of culture, the number of proliferated cells in the fluffy hydroxyapatite/polylactic acid composite scaffold was significantly more than that in the traditional hydroxyapatite/polylactic acid composite scaffold (P<0.01).(4) After 7 days of culture, FDA staining and scanning electric microscopy showed that cell-cell independent shape appeared in the traditional scaffold. A large number of cells appeared in the fluffy scaffold and grew into cell clusters with high cell activity, which formed a cell-fiber construction. These results indicate that this new type hydroxyapatite/polylactic acid composite scaffold is beneficial for cell entry and proliferation.
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Objective: To investigate the preparation process of polylactic acid-glycolic acid copolymer/ hydroxyapatite (PLGA/HA) microcarriers by electrostatic spraying method, and to elucidate the superiority of PLGA/HA microcarriers. Methods: The PLGA/HA microcarriers were prepared by electrostatic spraying method using nano-HA (20 nm, 99.9%) and PLGA (LA/GA = 50/50, Mw30k), and the influence of different concentrations (1%, 3%, 5%) and different voltages (4. 0, 4. 5, > 5. 0 kV) of HA in the morphology of the microcarriers was investigated and the best ball making parameters were obtained. The PLGA microcarriers were used as PLGA group, PLGA+1%HA as 1% PLGA/HA group, PLGA + 3% HA as 3% PLGA/HA group, PLGA+ 5% HA as 5% PLGA/HA group, and the simple cells were used as blank control group. The characteristics of PLGA/HA microcarriers were detected by scanning electron microscope (SEM), cell proliferation test, cell fluorescence staining experiment, and Fourier transform infrared spectroscopy (FTIR). Results: The SEM results showed that the microcarrier particles were uniform, all of them were elliptical or circular, without abnormal shape spheres, with smooth surface, without sharp edges, adhesion between the spheres and aggregation, and there were no significant differences between the different concentrations of microcarriers. The cell proliferation test results showed that the order of adhesion cells was 5% PLGA/HA group > 3% PLGA/HA group > 1% PLGA/HA group > PLGA group > blank control group (P<0. 05); the number of cells was increased with the increasing of HA concentration; the microcarriers in 5% PLGA/HA group had the best cell affinity and the microcarriers had no cytotoxity. The cell fluorescence staining experiment showed that the MC3T3-E1 cells adhered well on the microcarriers. The FTIR analysis results showed that HA characteristic absorption peak was observed, indicating that the composite microcarrier contained PLGA and HA. Conclusion: The preparation process of PLGA/ HA microcarriers is successfully established by electrostatic spraying method. The method is simple and convenient to operate, and has excellent ball-making effect. It has broadly application prospects in bone tissue engineering.
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Objective: To observe the effect of vascular endothelial growth factor/polylactide-polyethyleneglycol-polylactic acid copolymer/basic fibroblast growth factor (VEGF/PELA/bFGF) mixed microcapsules in promoting the angiogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods: The BMSCs were isolated by the method of whole bone marrow adherent, and sub-cultured. The passage 3 BMSCs were identified by Wright-Giemsa staining and flow cytometry, and used for subsequent experiments. VEGF/PELA/bFGF (group A), PELA/bFGF (group B), VEGF/PELA (group C), and PELA (group D) microcapsules were prepared. The biodegradable ability and cytotoxicity of PELA microcapsule were determined，and the slow-released ability of VEGF/PELA/bFGF mixed microcapsules was measured. The passage 3 BMSCs were co-cultured with the extracts of groups A, B, C, and D, separately. At 1, 3, 7, 14, and 20 days after being cultured, the morphological changes of induced BMSCs were recorded. At 21 days, the induced BMSCs were tested for DiI-labeled acetylated low density lipoprotein (Dil-ac-LDL) and FITC-labeled ulex europaeus agglutinin I (FITC-UEA-I) uptake ability. The tube-forming ability of the induced cells on Matrigel was also verified. The differences of the vascularize indexes in nodes, master junctions, master segments, and tot.master segments length in 4 groups were summarized and analyzed. Results: The isolated and cultured cells were identified as BMSCs. The degradation time of PELA was more than 20 days. There was no significant effect on cell viability under co-culture conditions. At 20 days, the cumulative release of VEGF in the mixed microcapsules exceeded 95%, and the quantity of bFGF exceeded 80%. The morphology of cells in groups A, B, and C were changed. The cells in groups A and B showed the typical change of cobble-stone morphology. The numbers of double fluorescent labeled cells observed by fluorescence microscope were the most in group A, and decreases from group B and group C, with the lowest in group D. The cells in groups A and B formed a grid-like structure on Matrigel. Quantitative analysis showed that the differences in the number of nodes, master junctions, master segments, and tot.master segments length between groups A, B and groups C, D were significant ( P0.05). Conclusion: VEGF/PELA/bFGF mixed microcapsules have significantly ability to promote the angiogenic differentiation of rat BMSCs in vitro.
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Objective@#To investigate whether poly (lactic-co-glycolic acid) (PLGA) as protein delivery vehicles that encapsulate CC chemokine receptor 5 antibody (anti-CCR5) has more suppressive function on macrophages than single anti-CCR5 in mouse endometriosis model.@*Methods@#The PLGA/anti-CCR5 nanoparticles were synthesized. The cumulative release of anti-CCR5 from PLGA/anti-CCR5 nanoparticles was evaluated. The mouse endometriosis model was established and divided into control group, anti-CCR5 group and PLGA/anti-CCR5 group. Meanwhile, ectopic endometrial cells (EEC) and macrophages isolated from peritoneal fluid were cultured in vitro. Flow cytometry was used to detect the proportion of macrophages in the peritoneal fluid of each group. The secretion of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in each group were determined by ELISA. The proliferation and infiltration of EEC were detected by 5-bromodeoxyuridine proliferation kit and matrigel invasion kit.@*Results@#The PLGA/anti-CCR5 nanoparticles were successfully synthesized. The mouse endometriosis model was established and the EEC and macrophages were cultured. Compared with the anti-CCR5 without nanoparticles, the bioconjugate PLGA/anti-CCR5 nanoparticles could control the release of anti-CCR5 from day 3 to day 24. The proportion of macrophages in PLGA/anti-CCR5 group were gradually reduced compared with those in anti-CCR5 group (P<0.01), the ratios of day 7 [(4.5±1.5)%] and day 3 [(6.3±0.6)%], day 14 [(2.6±0.7)%] and day 7 were significantly different (P<0.01 and P<0.05). PLGA/anti-CCR5 reduced IL-10 and TGF-β levels relative to anti-CCR5 (P<0.01),and decreased gradually on day 3, day 7, and day 14 (P<0.01). Anti-IL-10+anti-TGF-β could reduce the proliferation [(70.8±7.6)%] and invasion ability [(50.2±9.1)%] of EEC (P<0.05).@*Conclusions@#In mouse endometriosis model, PLGA/anti-CCR5 may inhibit the proliferation and invasion of EEC by inhibiting the secretion of IL-10 and TGF-β by macrophages, suggesting that it provide a new idea for the treatment of clinical endometriosis.
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Objective To investigate whether poly (lactic?co?glycolic acid) (PLGA) as protein delivery vehicles that encapsulate CC chemokine receptor 5 antibody (anti?CCR5) has more suppressive function on macrophages than single anti?CCR5 in mouse endometriosis model. Methods The PLGA/anti?CCR5 nanoparticles were synthesized. The cumulative release of anti?CCR5 from PLGA/anti?CCR5 nanoparticles was evaluated. The mouse endometriosis model was established and divided into control group, anti?CCR5 group and PLGA/anti?CCR5 group. Meanwhile, ectopic endometrial cells (EEC) and macrophages isolated from peritoneal fluid were cultured in vitro. Flow cytometry was used to detect the proportion of macrophages in the peritoneal fluid of each group. The secretion of interleukin 10 (IL?10) and transforming growth factor β (TGF?β) in each group were determined by ELISA. The proliferation and infiltration of EEC were detected by 5?bromodeoxyuridine proliferation kit and matrigel invasion kit. Results The PLGA/anti?CCR5 nanoparticles were successfully synthesized. The mouse endometriosis model was established and the EEC and macrophages were cultured. Compared with the anti?CCR5 without nanoparticles, the bioconjugate PLGA/anti?CCR5 nanoparticles could control the release of anti?CCR5 from day 3 to day 24. The proportion of macrophages in PLGA/anti?CCR5 group were gradually reduced compared with those in anti?CCR5 group (P<0.01), the ratios of day 7 [(4.5±1.5)%] and day 3 [(6.3±0.6)%], day 14 [(2.6±0.7)%] and day 7 were significantly different (P<0.01 and P<0.05). PLGA/anti?CCR5 reduced IL?10 and TGF?β levels relative to anti?CCR5 (P<0.01),and decreased gradually on day 3, day 7, and day 14 (P<0.01). Anti?IL?10+anti?TGF?β could reduce the proliferation [(70.8 ± 7.6)% ] and invasion ability [(50.2 ± 9.1)% ] of EEC (P<0.05). Conclusions In mouse endometriosis model, PLGA/anti?CCR5 may inhibit the proliferation and invasion of EEC by inhibiting the secretion of IL?10 and TGF?β by macrophages, suggesting that it provide a new idea for the treatment of clinical endometriosis.
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Polylactic acid is synthesized indirectly by the polymerization method, according to the standard GB/T 16886.18-2011, the evaluation parameters and methods about chemical characterization of polylactic acid have been established. By using rigorous and comprehensive comparative analysis, the chemical equivalency of domestic and imported polylactic acid materials has been proved, along with the "Medical Device Biology Evaluation and Review Guide", paving the way of using domestic polylactic acid in implantable medical devices.
Subject(s)
Equipment and Supplies , Lactic Acid , Polyesters , Chemistry , PolymersABSTRACT
Objective: To prepare celecoxib-loaded micelles with polyethylene glycol monomethyl ether-polylactic acid ( mPEG-PLA) block copolymer as the carrier material and evaluate the physical and chemical properties .Methods:Celecoxib-loaded micelles were prepared by a film dispersion method .The micelle formula and preparation process were screened by single factor experiment and further optimized by Box-Behnken response surface method .The physical and chemical properties of celecoxib-loaded micelles such as microscopic morphology , particle size distribution and zeta potential were evaluated .The in vitro drug release of celecoxib-loaded mi-celles was investigated by dynamic membrane dialysis .Results:Celecoxib-loaded micelles prepared according to the optimized formula showed the following properties:the particle size distribution was (35.6 ±15.1) nm, PdI was (0.152 ±0.05), and the zeta potential was (-24.6 ±2.9) mV.In 0.5％SDS phosphate buffered saline (pH 6.8), the in vitro cumulative release of celecoxib-loaded mi-celles reached up to 81 .5％in 24 h.Conclusion:It is simple and feasible to prepare celecoxib-loaded micelles by the thin film dis-persion method .
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Objective To prepare the biodegradable polylactic acid glycolic acid (PLGA) copolymer.encapsulated vascular endothelial growth factor(VEGF) loaded fluorescent controlled release sub-microspheres,to understand the efficiency of microspheres loading and releasing VEGF and to observe in vitro microspheres degradation.Methods VEGF-loading PLGA sub-microspheres were prepared by the two-phase solvent evaporation method,the in vitro degradation of fluorescent microspheres was observed by the laser confocal scanning electron microscopy.The drug loading efficiency and drug release curve were observed by ELISA.Results The VEGF loading PLGA fluorescent microspheres were successfully prepared by using the two-phase solvent evaporation method.The microspheres morphology was normal by using the scanning electron microscope and laser confocal microscope.The particle size was 0.5-1.0 μm with the laser particle size analyzer.The distribution was homogeneous.The VEGF loading rate and encapsulation rate detected by the quantitative ELISA were 3.91％ and 51.42 ％ respectively.The fluorescent microscope observed their slow degradation.The VEGF gentle release was detected by the quantitative ELISA,which showing linear zero order release trend.Conclusion The drug loading efficiency of VEGF-loading PLGA microspheres with 0.5-1.0 μm diameter is higher with linear zero order release,which can be directly observed by fluorescent light.
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Objective To evaluate the effect of two polymer membranes, polyhydroxyalkanoates(PHA)and polylactic acid(PLA)during glaucoma filtration surgery(GFS),and to evaluate the morphology of membranous PHA after interlamellar implantation. Methods Twenty-eight New Zealand white rabbits were chosen and twenty-four of them were randomly divided into 6 groups(n=4):the PHA-low group,PHA-high group,PLA-low group,PLA-high group,positive control group(MMC group)and blank control group. The rabbits in each group received GFS. The corresponding polymer membranes were implanted under the scleral flap,while the MMC group was treated with 0.2 mg/mL mitomycin C(MMC) for 3 minutes,and the blank control group was treated without extra drugs. The intraocular pressure(IOP)was examined at 0 d,1 d, 3 d, 7 d, 14 d, 28 d and 84 d after GFS. The corneal layers of four rabbits were implanted with PHA membranes and the corneal morphological changes were observed after 84 d. Results The IOP of the PHA-low and PLA-high groups was lower than that of the blank control group at 84 d after GFS(P < 0.05),and was similar with that of the MMC group(P> 0.05). Morphological studies showed that there were no collagenous fibers filling in the duct, and the collagenous fibers around the membranes were generally arranged in parallel. There were no obvious changes in the peripheral collagen structure after implantation of PHA membranes between the corneal layers. Conclusions Application of PHA and PLA membranes during GFS in rabbits may maintain the level of IOP,and the effect is similar with MMC. The mechanism may be achieved through the mechanical blocking of fibrous tissue.
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Objective: To establish a method using gas chromatography for the determination of the residual chloroform in the medical polylactic acid membrane. Methods: The direct aqueous injection gas chromatographic method was established for the determination using RESTEK RTX capillary-column chromatography with the electron capture detector(ECD) at 270 ℃ and with the column at 85 ℃,maintained for 3 min. The split ratio of sampling was 10∶1. The injector temperature was 200 ℃. The high purity nitrogen was used as the carrier gas with the flow of 1. 0 ml /min. The injection volume was 1 μl. Results: The calibration curve showed a good linearity within the range of 25-2 000 ng /ml (r = 0. 999 9). The limit of detection was 1. 50 ng /ml,and the limit of quantitation was 4. 62 ng /ml. The average recovery rate was 98. 35％,RSD = 1. 98％. Conclusion: Gas chromatography is sensitive and accurate for the determination of the residual chloroform in the medical polylactic acid membrane.
ABSTRACT
Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. Currently, adhesion barriers are used in many surgical interventions and while they have become a subject of an increasing interest for their effectiveness, there has not been any reports on the adverse effects of these anti-adhesion agents. Three different types of antiadhesive agents (SurgiWrap®, Guardix-Sol®, Interceed®) have been noted as effective in adhesion prevention. We report, with a review of literature, on a patient who had a foreign body reaction that caused a side effect of anti-adhesion SurgiWrap® after thyroid surgery.