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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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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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To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21) %, (11.71 ± 0.39) %, (15.41 ± 0.40) %, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64) % and (5.66 ± 0.07) % curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres.
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PURPOSE: This study was designed to compare the bond regeneratiom effects of treatment using silk fibroin membrane ( Nanogide-S (R)) resorbable barrier with control group treated by polyactic acid / polylacticglycolic acid membrane(Biomesh (R) ) METHODS:44 severe bone loss on extraction socket from 44 patients were used in this study. In experimental group 22 sites of them were treated by silk fibrin membrane as and the other 22 sites were treated by polyactic acid/ polylacticglycolic acid membrane as a control group. Clinical parameters including recovered bone width, length and radiographic parameter of vertical length were evlauated at base line and 3 months after surgery. RESULTS: 1) Severe bone width, length was significantlly decreased in two group. 2) Bone width, length was significantlly decreased in two group. 3) Decreased bone width, length and radiographic examination differences between group. CONCLUSIONS: On the basis of these results, silk fibrin resorbable membrane has similar bone regeneration ability to polyactic acid / polylacticglycolic acid membrane in guided bone regeneration for severe bone loss defect on extraction socket.
Subject(s)
Humans , Bone Regeneration , Fibrin , Fibroins , Lactic Acid , Membranes , Polyglycolic Acid , Regeneration , SilkABSTRACT
Objective To observe the effects of porous polylactic acid/polyglycolic acid copolymer(PLGA) filling into extraction socket on the regeneration of alveolar bone in rats.Methods Sixty male Wistar rats were divided into experimental group and control group(n=30).PLGA scaffold was immediately implanted in the mandibular incisor root sockets after removal of incisor teeth.Soft X-ray photography,structural observation,light microscopy were used to evaluate the effects of composite on bone healing in a rat tooth extraction socket.Results The relative lengths of residual alveolar ridge in the experimental group 4,8 weeks after operation were shorter than that in the control group,and there were significant differences between the experimental group and the control group(P