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1.
Zhonghua Fu Chan Ke Za Zhi ; 54(10): 680-686, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31648444

RESUMO

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 ß (TGF-ß) 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-ß 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-ß 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-ß by macrophages, suggesting that it provide a new idea for the treatment of clinical endometriosis.


Assuntos
Endometriose/tratamento farmacológico , Ácido Láctico/química , Nanopartículas/uso terapêutico , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Receptores CCR5/uso terapêutico , Animais , Endometriose/imunologia , Feminino , Humanos , Camundongos , Nanopartículas/química , Resultado do Tratamento
2.
Int J Pharm ; 570: 118686, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31513874

RESUMO

Supercritical Emulsion Extraction (SEE) and Supercritical assisted Liposome formation (SuperLip), use dense gases such as carbon dioxide (dCO2) to fabricate advanced micro/nanocarriers. SEE uses dCO2 to extract solvent from the oily phase of an emulsion and obtain biopolymer microbead; For this study, poly-Lactic Acid (PLA) microbeads of 1 ±â€¯0.2 µm in mean size loaded at 1 µg/mgPLA with Rhodamine B (ROD) were prepared by SEE; the beads showed a solvent residue lower than 10 ppm and encapsulated the fluorochrome with an efficiency of 90%. SuperLip uses dCO2 to enhance lipid/ethanol/water mixing and to promote the ethanol extraction from liposome suspension. In this case, phosphatidyl-choline (PC) vesicles with a mean size of 0.2 ±â€¯0.05 µm and loaded with Fluorescein Iso-ThioCyanate (FITC) at 8 µg/mgPC were prepared; small unilamellar structure was observed for all the vesicles with FITC encapsulation efficiency of 80%. Ethanol residue of 50 ppm was measured in all the liposome suspensions. The bioavailability of microbeads and nanoliposomes was assessed through incubation with human monocytes previously isolated from healthy donors' blood. A specifically optimized protocol that allowed their quenching on the cell surface was developed to monitor by flow cytometer assay only the cell population that effectively internalized the carriers. When microbeads were tested, the percentage of alive internalizing monocytes was of about 30%. An internalization of 96.1 ±â€¯21% was, instead, obtained at dosage of 0.1 mg/mL for nanoliposomes. In this last case, monocytes showed a vitality of almost 100% after vesicles internalization at all the concentrations studied; on the other hand, cell apoptosis progressively increased in a dose/response manner, after polymer microbeads phagocytosis. The proposed data suggested that dCO2 technologies can be reliably used to fabricate intracellular carriers.


Assuntos
Dióxido de Carbono/química , Lipossomos/química , Monócitos/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Disponibilidade Biológica , Células Cultivadas , Química Farmacêutica/métodos , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Emulsões/química , Citometria de Fluxo/métodos , Humanos , Microesferas , Tamanho da Partícula , Poliésteres/química , Ácido Poliglicólico/química , Rodaminas/química , Solventes/química , Suspensões/química
3.
Nanoscale ; 11(39): 18209-18223, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31560010

RESUMO

Rheumatoid arthritis (RA) is a degenerative joint disease caused by autoimmunity; for the effective treatment of RA while avoiding the side effects of conventional drugs, we have proposed a new therapeutic strategy to eliminate the inflammatory response in RA by regulating the immune system that promotes the transformation of M1-type macrophages to M2-type macrophages. Herein, we designed and synthesized a core-shell nanocomposite (QRu-PLGA-RES-DS NPs), which showed an effective therapeutic effect on RA by accurately inducing the polarization of M2 macrophages. In this system, the quadrilateral ruthenium nanoparticles (QRuNPs) with a photothermal effect were utilized as a core and the thermosensitive molecular poly (lactic-co-glycolic acid) (PLGA) modified with the targeted molecule dextran sulfate (DS) was employed as a shell. Then, the nanocarrier QRu-PLGA-DS NPs effectively improved the water solubility and targeting of resveratrol (RES) through self-assembly. Therefore, the QRu-PLGA-RES-DS NPs significantly enhanced the ability of RES to reverse the M1 type macrophages to the M2 type macrophages through an accurate release. In vivo experiments further demonstrated that the QRu-PLGA-RES-DS NPs could effectively accumulate in the lesion area with an exogenous stimulus, and this significantly enhanced the transformation of the M2 type macrophages and decreased the recruitment of the M1 type macrophages. Furthermore, the QRu-PLGA-RES-DS NPs effectively treated RA by eliminating the inflammatory response; in addition, photoacoustic imaging (PA) of the QRu NPs provided image guidance for the distribution and analysis of nanomedicine in inflammatory tissues. Hence, this therapeutic strategy promotes the biological applications of Ru-based nanoparticles in disease treatment.


Assuntos
Hipertermia Induzida , Macrófagos/metabolismo , Nanocompostos , Fototerapia , Resveratrol , Febre Reumática/terapia , Animais , Células Endoteliais da Veia Umbilical Humana , Humanos , Macrófagos/patologia , Camundongos , Nanocompostos/química , Nanocompostos/uso terapêutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Células RAW 264.7 , Resveratrol/farmacocinética , Resveratrol/farmacologia , Febre Reumática/metabolismo , Febre Reumática/patologia , Rutênio/química , Rutênio/farmacocinética , Rutênio/farmacologia
4.
J Mater Sci Mater Med ; 30(9): 105, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31494718

RESUMO

Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.


Assuntos
Substitutos Ósseos/uso terapêutico , Cerâmica/uso terapêutico , Fraturas Ósseas/terapia , Luz , Ácido Poliglicólico/uso terapêutico , Crânio/lesões , Cicatrização/efeitos dos fármacos , Animais , Substitutos Ósseos/química , Substitutos Ósseos/efeitos da radiação , Transplante Ósseo/métodos , Cimentação/métodos , Cerâmica/química , Terapia Combinada , Masculino , Teste de Materiais , Osteogênese/efeitos dos fármacos , Osteogênese/efeitos da radiação , Fototerapia/métodos , Ácido Poliglicólico/química , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Crânio/efeitos da radiação , Engenharia Tecidual
5.
J Mater Sci Mater Med ; 30(8): 93, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31392433

RESUMO

To enhance the bioavailability of protein therapeutants and improve the stability of storage and delivery, a series of branched amphiphilic block copolymers consisting of cholic acid (CA) initiated poly(D,L-lactide-co-glycolide) (CA-PLGA) and water-soluble polyethyleneimine cross-linked polyethylene glycol (PEI-PEG) denoted as CA-PLGA-b-(PEI-PEG) were synthesized and characterized. CA-PLGA-b-(PEI-PEG) presented low cytotoxicity by MTT and cck-8 assay. The cationic CA-PLGA-b-(PEI-PEG) micelles (diameter about 100 nm and zeta potential 34-61 mV) were prepared through self-assembly method, and complexed with insulin via electrostatic interaction to obtain nanoscale micelle/insulin complexes. The micelle/insulin complexes-loaded CA-PLGA microspheres (MIC-MS, 10.4 ± 3.85 µm) were manufactured by employing a double emulsion (W1/O/W2) method. The in vitro insulin release behavior and in vivo hypoglycaemic effect of MIC-MS on streptozotocin (STZ) induced diabetic rats were compared with those of the insulin-loaded CA-PLGA microspheres (INS-MS, 7.8 ± 2.57 µm). The initial burst in vitro release of MIC-MS was markedly lower than that of INS-MS (P < 0.01), and the pharmacological availability of MIC-MS via subcutaneous administration was 148.9% relative to INS-MS. Therefore, the cationic CA-PLGA-b-(PEI-PEG) micelles can effectively increase the bioavailability of insulin in CA-PLGA microspheres and can be considered as a potential protein carrier.


Assuntos
Portadores de Fármacos , Microesferas , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Poliglactina 910/química , Animais , Cátions , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Células MCF-7 , Masculino , Micelas , Nanopartículas/química , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoimina/síntese química , Polietilenoimina/química , Ácido Poliglicólico/química , Polímeros/síntese química , Polímeros/química , Ratos , Ratos Sprague-Dawley , Estreptozocina
6.
J Pharm Pharmacol ; 71(10): 1497-1507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385295

RESUMO

OBJECTIVE: To evaluate the impact of PEG content on poly(lactic-co-glycolic acid) (PLGA) NP physicochemical properties, hydrophobic drug release (rifampicin as a model drug) and human serum protein binding. METHODS: Rifampicin loaded and unloaded nanoparticles with PEG content of 0-17% (w/w) were prepared by an emulsification-evaporation technique. Nanoparticles were characterized for size, zeta potential and morphology. PEGlyation was confirmed using proton nuclear magnetic resonance (1H NMR). Fluorescence spectroscopy and dynamic light scattering were used to determine nanoparticle-protein binding, binding constants and stability of nanoparticles in human serum, respectively. Drug loading and release were determined by UV-VIS spectroscopy and drug release data was mathematically modelled. KEY FINDINGS: A NP PEG content of 17% w/w significantly retarded release of rifampicin from PLGA NPs and altered kinetics of drug release. Stern-Volmer (Ksv) protein binding constants decreased upon PEG incorporation. A 2% w/w PEG was sufficient to significantly reduce protein binding extent to PLGA NPs and maintain particle size distributions. CONCLUSION: The ability to fine tune drug release and formation of protein corona around nanoparticles is crucial to formulation scientists. This study suggests that PLGA NPs with low PEG content might be suitable for extended circulation and rapid drug release and that higher PEG content retards hydrophobic drug release.


Assuntos
Nanopartículas/química , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Albumina Sérica Humana/química , Soro/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética/métodos , Tamanho da Partícula , Ácido Poliglicólico/química
7.
Artif Cells Nanomed Biotechnol ; 47(1): 3438-3447, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31411066

RESUMO

Gliomas are the most common brain tumors in humans. Different chemotherapeutics are available to treat gliomas. However, they are costly and pose numerous side effects. The development of nanocomposite based on chemotherapeutic drug and metallic nanoparticle loaded with polymer could be highly useful against glioma. In this study, carmustine loaded with gold NPs and linked with PLGA-PSPE was produced as a bio-nanocomposite and its efficacy in treating glioma and burn wound were investigated. The synthesized biocomposite was characterized by biophysical techniques. It was observed that the synthesized composite was hexagonal and crystalline nature. TGA analysis showed that the particle had good combustible property. Interestingly, the Cm-Au-PLGA-PSPE composite had exhibited remarkable anti-tumor property against U251 human glioma. The flow cytometry showed a greater increase in the apoptosis rate (62.31%) of glioma cells exposed to the bio-nanocomposite. In addition, a greater reduction in the viability of U251 cells was recorded following treatment with Cm-Au-PLGA-PSPE composite. Quick healing of the heart, liver, spleen, lung and kidney tissue wounds in mouse was noticed with Cm-Au-PLGA-PSPE composite treatment. This study concludes that the newly produced Cm-Au-PLGA-PSPE composite would be a promising alternative in treating human gliomas and associated wounds with increased biomedical applications.


Assuntos
Neoplasias Encefálicas/patologia , Carmustina/química , Glioma/patologia , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Cicatrização/efeitos dos fármacos , Carmustina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Composição de Medicamentos , Humanos , Cuidados de Enfermagem
8.
Colloids Surf B Biointerfaces ; 181: 935-942, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382343

RESUMO

This study aimed to optimize Cymbopogon citratus essential oil loaded into PLGA-nanoparticles by investigating the effect of processing variables (sonication time, ultrasound power, and essential oil/polymer ratio) on encapsulation efficiency and particle mean hydrodynamic diameter using Box-Behnken design. Nanoparticles were prepared by an emulsification/solvent diffusion method and physicochemically characterized by FTIR, DSC and TGA/DTA. Cytotoxicity was evaluated in human HaCat keratinocytes by WST-1 and LDH assays. The optimized formulation had a hydrodynamic mean diameter of 277 nm, a polydispersity index of 0.18, a Zeta potential of -16 mV and an encapsulation efficiency of 73%. Nanoparticle characterization showed that only citral was incorporated in nanocarriers, with some amount adsorbed on their surface, and highlighted the potential in increasing the oil thermal stability. The drug release profile demonstrated a biphasic pattern with a substantial sustained release depending on diffusion from the polymeric matrix. Toxicity effects on cell viability of pure essential oil at low concentrations were significantly eliminated when encapsulated. Results revealed the ability of PLGA-nanoparticles to improve essential oil physicochemical characteristics, by controlling release and reducing toxicity, suggesting their potential use in pharmaceutical preparations.


Assuntos
Nanopartículas/química , Óleos Voláteis/farmacologia , Ácido Poliglicólico/química , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cymbopogon/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Cinética , Óleos Voláteis/química , Tamanho da Partícula , Propriedades de Superfície
9.
Drug Deliv ; 26(1): 595-603, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31195837

RESUMO

With high morbidity and death rates, liver cancer has become one of the most common cancers in the world. But, most chemotherapeutic anticancer drugs have high toxicity as well as low specificity. To improve the treatment modalities and enhance the therapeutic effect of liver cancer, a brand new liver-targeting nanoparticle (NP), Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5 F)-loaded cholic acid (CA)-functionalized star-shaped poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-lactobionic acid (LA) (5 F-loaded CA-PLGA-PEG-LA), was developed. The particle size, zeta potential, size distribution, surface morphology, drug loading content, drug encapsulation efficiency and drug release of 5 F-loaded NPs were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be internalized by HepG2 cells. Furthermore, the cellular uptake efficiency of coumarin 6-loaded CA-PLGA-PEG-LA NPs was much better in compare with that of CA-PLGA-PEG and CA-PLGA NPs. Moreover, LA-conjugated NPs (CA-PLGA-PEG-LA NPs) enhanced fluorescence of HepG2 cells via ligand-mediated endocytosis. The antitumor effects of 5 F-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted 5 F-loaded CA-PLGA-PEG-LA NPs were significantly superior to free 5 F and 5 F-loaded CA-PLGA-PEG NPs. All the results indicated the 5 F-loaded CA-PLGA-PEG-LA NPs can be employed as a novel potentially targeting drug delivery system for liver cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Ácido Cólico/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Lactatos/química , Ácido Láctico/química , Camundongos , Camundongos Nus , Tamanho da Partícula , Polietilenoglicóis/química , Ácido Poliglicólico/química
10.
J Cancer Res Ther ; 15(3): 480-490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169208

RESUMO

Objective: The aim of the study to develop surface modified targeted moiety α-tocopherol (α-t) encapsulated with 5-fluorouracil (5-FU)-poly-D, L-lactic-co-glycolic acid nanoparticles (PLGA NPs) toward the anticancer activity against oral squamous cell carcinoma (OSCC). Materials and Methods: 5-FU was conjugated with the polymer, PLGA by ionic cross-linking and α-tocopherol use as a functionalized surface moiety. Characterization, drug entrapment efficiency, and in-vitro drug release system were optimized at different pH 7.4 and pH 4.5. The in-vitro cell was performed to optimize the anticancer activity through MTT assay and apoptotic staining assay was also performed by flow cytometry to evaluate the cellular apoptotic activity and cellular uptake. Results: The particle size was distributed within an average range of 145-162 nm, the polydispersity index values lie 0.16-0.30, and the surface charge was at the negative side, -17mV to -23mV. The in vitro drug release system showed more sympathetic situation at pH 7.4 as compared to pH 4.5, for targeted NPs, approximately 86% and 69%, respectively. The non-targeted 5-FU-PLGA NPs showed drug release of 83% and 64% at pH 7.4 and 4.5 subsequently. In vitro anticancer activity confirmed the intense inhibition by α-t-FU-PLGA NPs of 79.98% after 96 h treatment of SCC15 cells and confirmed the steady-state inhibition of 83.74% after 160 h incubation in comparison to 5-FU-PLGA NPs. Subsequently, the early apoptosis, 27.98%, and 16.45%, and late apoptosis, 47.29%, and 32.57%, suggested the higher apoptosis rate in targeted NPs against OSCC. Conclusions: The surface modified α-t-FU-PLGA NP was treated over SCC15 cells, and the oral cancer cells have shown the high intensity of cellular uptake, which confirmed that the target moiety has successfully invaded over the surface of cancer cells and shown advanced targeted delivery against OSCC.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Portadores de Fármacos , Fluoruracila/administração & dosagem , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , alfa-Tocoferol , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Neoplasias Bucais , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Propriedades de Superfície , alfa-Tocoferol/química
11.
Eur J Pharm Biopharm ; 141: 70-80, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082511

RESUMO

Upon intravenous administration of nanoparticles (NP) into the bloodstream, proteins bind rapidly on their surface resulting in a formation of a so-called 'Protein Corona'. These proteins are strongly attached to the NP surface and provide a new biological identity which is crucial for the reaction at the nano-biointerface. The structure and composition of the protein corona is greatly determined by the physico-chemical properties of the NP and the characteristics of the biological environment. The overall objective of this study was to characterize the role of NP size/surface curvature and PEGylation on the formation of the protein corona. Therefore, we prepared NP in a size of 100 and 200 nm using the biodegradable polymers poly(DL-lactide-co-glycolide) (PLGA) and poly(DL-lactide-co-glycolide)-co-polyethylene glycol diblock (PLGA-PEG) and subsequently incubated them with fetal bovine serum (FBS) to induce the formation of a protein corona. After removal of unbound protein, we employed different analytical approaches to study the corona in detail. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) was performed to gain a first impression about amount and composition of the corona proteins. Identification was carried out after tryptic in-solution digestion and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In addition, we successfully established the Bradford protein assay as a suitable colorimetric method to quantify total adsorbed protein amount after alkaline hydrolysis of PLGA based NP. Our results revealed that protein adsorption on PLGA- and PLGA-PEG-NP didn't depend on NP size within the range of 100 and 200 nm. PEGylation led to a significant reduced amount of bound proteins. The depletion of proteins which are involved in immune response was remarkable and indicated a prolonged circulation time in body.


Assuntos
Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Coroa de Proteína/química , Adsorção/efeitos dos fármacos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Propriedades de Superfície/efeitos dos fármacos
12.
Colloids Surf B Biointerfaces ; 181: 149-157, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128515

RESUMO

Whey-derived alpha-casozepine bioactive peptide (YLGYLEQLLR) was associated with previously optimized guar-gum film-PLGA nanoparticles, aiming to increase both stability across gastrointestinal tract and permeability across absorptive epithelia. Oral films associated with nanoparticles (FNp) enhance buccal absorption along with protection of carried bioactive molecules that are swallowed, with inherent increase of bioavailability. None of developed formulations induced significant loss of cell viability. Permeability across both buccal and intestinal cell barriers was enhanced when alpha-casozepine was carried by FNp system, when compared with film and nanoparticles alone, in a simulated gastrointestinal tract environment. Moreover, differences in permeability profile across buccal and intestinal epithelia were in accordance with the slower erosion of PLGA nanoparticles in a media of neutral pH, resembling oral cavity conditions, and a faster erosion in acidic conditions, as occurs in stomach, as observed by a continuous analysis of nanoparticle morphology over 980 min by atomic force microscopy. Additionally, apparent permeability of alpha-casozepine across TR146 human buccal carcinoma cells and Caco-2/HT29-MTX co-culture, carried by FNp was indeed superior when compared with peptide loaded in PLGA nanoparticles and in films alone or with free peptide control solution. Both FNp and PLGA nanoparticles alone enhanced the permeability of relaxing peptide compared with guar-gum films alone. An increased tongue adhesion when PLGA nanoparticles were added to the guar-gum films was also observed. Developed formulations improved both buccal an intestinal absorption of carried bioactive molecules without compromising cell viability.


Assuntos
Caseínas/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Fragmentos de Peptídeos/química , Ácido Poliglicólico/química , Administração Oral , Caseínas/administração & dosagem , Caseínas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Mitocôndrias/efeitos dos fármacos , Nanopartículas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Ácido Poliglicólico/administração & dosagem , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
J Agric Food Chem ; 67(18): 5113-5121, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31013074

RESUMO

Astaxanthin, a hydrophobic carotenoid found in marine plants and animals, is claimed to exhibit various beneficial biological activities. Its use as a nutraceutical in foods, however, is currently limited by its low water-solubility and poor bioavailability. The goal of this paper was to fabricate astaxanthin-loaded colloidal particles to overcome these challenges. Astaxanthin was encapsulated in poly(lactic- co-glycolic acid) (PLGA) nanoparticles coated with chitosan oligosaccharides (COS). The properties of the loaded nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The influence of PLGA properties on the loading capacity, water solubility, stability, and release of the astaxanthin were determined. The nanoparticles were smooth spheres with mean particle diameters around 150 nm and positive surface potentials (ζ = +30 mV). The encapsulation efficiency (>85%) and loading capacity (>15%) of the astaxanthin in the nanoparticles was relatively high. X-ray analysis suggested that the encapsulated astaxanthin was in an amorphous form. The nanoparticles had good dispersibility and stability in aqueous solutions, as well as high cytocompatibility. In vitro studies showed that the astaxanthin was released from the nanoparticles under simulated gastric and small intestinal conditions. Overall, our results suggest the core-shell nanoparticles developed in this study may be suitable for encapsulating this important nutraceutical in functional foods and cosmetics.


Assuntos
Quitosana/química , Nanopartículas/química , Oligossacarídeos/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Disponibilidade Biológica , Células CACO-2 , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Estabilidade de Medicamentos , Humanos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Solubilidade , Difração de Raios X , Xantofilas/química , Xantofilas/metabolismo
14.
J Mater Sci Mater Med ; 30(3): 34, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840138

RESUMO

Antimicrobial resistance to traditional antibiotics leads to a serious concern for medical care owing to ineffective antibiotic therapies. This study focused on the preparation of silver nanocomposites (AgNPs@Tob&PAGA) by modifying AgNPs with tobramycin (Tob) and carbohydrate polymer of poly(2-(acrylamido) glucopyranose) (PAGA). The enhanced antibacterial activities of nanocomposites against common pathogens of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were explored. The introduction of PAGA onto silver nanocomposites improved both citocompatibility and antibacterial activity. Compared with nude Tob, AgNPs@Tob&PAGA showed more fascinating antimicrobial effect against E. coli and S. aureus with about 20-fold increase in the antibacterial activity, simultaneously no detectable resistance was observed. Consequently, the silver nanocomposite as an antimicrobial agent presents promising prospects in the treatment of bacterial infections caused by antimicrobial resistant bacteria.


Assuntos
Antibacterianos/química , Farmacorresistência Bacteriana , Nanopartículas Metálicas/química , Nanocompostos/química , Ácido Poliglicólico/análogos & derivados , Prata/química , Animais , Materiais Biocompatíveis/química , Carboidratos/química , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Grafite , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Ácido Poliglicólico/química , Staphylococcus aureus/efeitos dos fármacos , Tobramicina/química
15.
J Mater Sci Mater Med ; 30(3): 33, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840143

RESUMO

We have evaluated the capability of a collagen/poly glycolic acid (PGA) scaffold in regeneration of a calvarial bone defects in rabbits. 4 bone critical size defects (CSD) were created in the calvarial bone of each rabbit. The following 4 treatment modalities were tested (1) a collagen/PGA scaffold (0.52% w/w); (2) the collagen/PGA scaffold (0.52% w/w) seeded with adipose-derived mesenchymal stem cells (AD-MSCs, 1 × 106 cells per each defect); (3) AD-MSCs (1 × 106 cells) no scaffold material, and (4) blank control. The rabbits were then divided into 3 random groups (of 5) and the treatment outcomes were evaluated at 4, 8 and 12 weeks. New bone formation was histologically assessed. Experimental groups were analyzed by CT scan and real-time PCR. Histological analysis of bone defects treated with collagen/PGA alone exhibited significant fibrous connective tissue formation at the 12 weeks of treatments (P ≤ 0.05). There was no significant difference between collagen/PGA alone and collagen/PGA + AD-MSCs groups. The results were confirmed by CT scan data showing healing percentages of 34.20% for the collage/PGA group alone as compared to the control group and no difference with collagen/PGA containing AD-MSCs (1 × 106 cells). RT-PCR analysis also indicated no significant differences between collagen/PGA and collagen/PGA + AD-MSC groups, although both scaffold containing groups significantly express ALP and SIO rather than groups without scaffolds. Although there was no significant difference between the scaffolds containing cells with non-cellular scaffolds, our results indicated that the Collagen/PGA scaffold itself had a significant effect on wound healing as compared to the control group. Therefore, the collagen/PGA scaffold seems to be a promising candidate for research in bone regeneration.


Assuntos
Regeneração Óssea , Osso e Ossos/patologia , Colágeno/química , Ácido Poliglicólico/química , Tecidos Suporte/química , Cicatrização , Tecido Adiposo/citologia , Animais , Materiais Biocompatíveis , Osso e Ossos/lesões , Diferenciação Celular , Linhagem da Célula , Condrócitos/citologia , Feminino , Fibroblastos/metabolismo , Consolidação da Fratura , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Engenharia Tecidual , Tomografia Computadorizada por Raios X
16.
Mol Pharm ; 16(2): 498-509, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30477303

RESUMO

Targeted delivery of vaccine has the potential to localize the therapeutic agent to a target tissue with minimum side-effects. This article presents the development of a model targeted immunotherapeutic approach that will harness effective T cell response. Here, we investigated the impact of a model nanoparticulate cancer vaccine on the immune system of in vivo mice models. The nanoparticles (NPs) were prepared by a double emulsification solvent evaporation technique. The anti-CD205 targeted formulations were obtained either through physical adsorption or a covalent conjugation method. The structural integrity of ovalbumin (OV) was confirmed by circular dichroism spectroscopy. Flow cytometry and enzyme-linked immunosorbent assay experiments were performed to evaluate T cell proliferation and cytokine secretion. Our results indicate that the antigen-adjuvant combined formulation induced more powerful responses compared to formulations with either of these alone. Wild-type balb/c mice immunized with the targeted poly (D,L-lactic- co-glycolic-acid) (PLGA) NPs encapsulated with OV and monophosphoryl lipid A (MP) induced profound secretion of antigen-specific IgG antibodies and cytokines and generation of memory T cells. OV specific T cell receptor transgenic OT1 mice showed the highest production of cytotoxic T cells and increased the secretion of cytokines upon immunization with the targeted OVMP formulations. The enhanced response might be attributed to the OV depot effect at the subcutaneous site of injection that triggered effective induction of dendritic cells activation and helper T cell differentiation in the lymph nodes. Therefore, the developed targeted PLGA-based delivery system could be utilized as a successful model vaccine in the future.


Assuntos
Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Nanopartículas/química , Ácido Poliglicólico/química , Animais , Vacinas Anticâncer/administração & dosagem , Células Cultivadas , Dicroísmo Circular , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/química , Linfócitos T/metabolismo
17.
Drug Deliv Transl Res ; 9(1): 76-84, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484256

RESUMO

Cutaneous leishmaniasis (CL) is an infectious, parasitic disease caused by the protozoan Leishmania. Amphotericin B (AMB) is a macrolide polyene antibiotic presenting potent antifungal and antileishmanial activity, but due to poor water solubility at physiological pH, side effects, and toxicity, its therapeutic efficiency is limited. In the present study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with AMB were generated to reduce drug toxicity and facilitate localized delivery over a prolonged time. AMB NPs were characterized for particle size, zeta potential, polydispersity index, and degree of aggregation. In vitro assessments demonstrated its sustained activity against Leishmania major promastigotes and parasite-infected macrophages. A single intralesional administration to infected BALB/c mice revealed that AMB NPs were more effective than AMB deoxycholate in terms of reducing lesion area. Taken together, these findings suggest that AMB NPs improve AMB delivery and can be used for local treatment of CL.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Poliésteres/química , Ácido Poliglicólico/química , Administração Tópica , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Modelos Animais de Doenças , Portadores de Fármacos/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Tamanho da Partícula , Células THP-1
18.
Colloids Surf B Biointerfaces ; 175: 281-290, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30551015

RESUMO

Biodegradable polymer based 'controlled release packaging' technology has ability to release packaging actives in controlled manner to prolong the food shelf-life. Currently available systems are not sufficiently capable of releasing multiple actives in sustainable fashion. Hence, the purpose of this study was to develop dual actives (antioxidant and antibacterial) loaded multilayered microparticles in one step and to release them at rates suitable for long-term inhibition of bacterial growth as well as lipid oxidation in food. In order to achieve this goal, 2 kinds of multilayered polymer particles made up of PLLA (Poly(l-lactic acid)) and PLGA (Poly(dl-lactic-co-glycolic acid) with varying viscosity were developed using emulsion solvent evaporation method. Surprisingly, low viscous PLGA resulted tri-layered particles (PLGA/PLLA/PLGA: shell/middle/core) instead of bi-layered (PLGA/PLLA: shell/core) particles as observed for high viscous PLGA. The mechanism of formation of tri-layered particles was investigated in detail. The outermost layer consisted of relatively more hydrophilic polymer PLGA along with benzoic acid (antibacterial) and the inner core comprised of hydrophobic polymer PLLA and tocopherol (antioxidant). Release study demonstrated that release rate of dual actives were significantly accelerated from tri-layered particles in comparison to bi-layered one and their release profiles can be well explained with the help of Ridger-Peppas model. Both sets of particles exhibited long-term antibacterial (against both Escherichia coli and Staphylococcus aureus) as well as antioxidant effect over a period of 60 days. The results show for the first time the feasibility of using multilayered microparticles to prolong the food shelf-life by simultaneous release of multiple actives.


Assuntos
Ácido Benzoico/farmacocinética , Liberação Controlada de Fármacos , Armazenamento de Alimentos/métodos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tocoferóis/farmacocinética , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Ácido Benzoico/química , Ácido Benzoico/farmacologia , Emulsões/química , Escherichia coli/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Reprodutibilidade dos Testes , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Fatores de Tempo , Tocoferóis/química , Tocoferóis/farmacologia
19.
PLoS One ; 13(11): e0206324, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30383798

RESUMO

Mucosal vaccine delivery systems have paramount importance for the induction of mucosal antibody responses. Two studies were conducted to evaluate immunogenicity of inactivated AIV antigens encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). In the first study, seven groups of specific pathogen free (SPF) layer-type chickens were immunized subcutaneously at 7-days of age with different vaccine formulations followed by booster vaccinations two weeks later. Immune responses were profiled by measuring antibody (Ab) responses in sera and lachrymal secretions of vaccinated chickens. The results indicated that inactivated AIV and CpG ODN co-encapsulated in PLGA NPs (2x NanoAI+CpG) produced higher amounts of hemagglutination inhibiting antibodies compared to a group vaccinated with non-adjuvanted AIV encapsulated in PLGA NPs (NanoAI). The tested adjuvanted NPs-based vaccine (2x NanoAI+CpG) resulted in higher IgG responses in the sera and lachrymal secretions at weeks 3, 4 and 5 post-vaccination when immunized subcutaneously. The incorporation of CpG ODN led to an increase in Ab-mediated responses and was found useful to be included both in the prime and booster vaccinations. In the second study, the ability of chitosan and mannan coated PLGA NPs that encapsulated AIV and CpG ODN was evaluated for inducing antibody responses when delivered via nasal and ocular routes in one-week-old SPF layer-type chickens. These PLGA NPs-based and surface modified formulations induced robust AIV-specific antibody responses in sera and lachrymal secretions. Chitosan coated PLGA NPs resulted in the production of large quantities of lachrymal IgA and IgG compared to mannan coated NPs, which also induced detectable amounts of IgA in addition to the induction of IgG in lachrymal secretions. In both mucosal and subcutaneous vaccination approaches, although NPs delivery enhanced Ab-mediated immunity, one booster vaccination was required to generate significant amount of Abs. These results highlight the potential of NPs-based AIV antigens for promoting the induction of both systemic and mucosal immune responses against respiratory pathogens.


Assuntos
Galinhas , Imunidade nas Mucosas , Imunogenicidade da Vacina/fisiologia , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/terapia , Doenças das Aves Domésticas/terapia , Vacinação , Administração Intranasal , Administração Oftálmica , Animais , Antígenos Virais/imunologia , Galinhas/imunologia , Galinhas/virologia , Composição de Medicamentos/métodos , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunização , Imunização Secundária/métodos , Imunização Secundária/veterinária , Vacinas contra Influenza/química , Vacinas contra Influenza/imunologia , Influenza Aviária/imunologia , Injeções Subcutâneas , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/imunologia , Membrana Mucosa/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/química , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Vacinação/métodos , Vacinação/veterinária , Vacinas de Produtos Inativados
20.
Artif Cells Nanomed Biotechnol ; 46(sup3): S481-S491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30299174

RESUMO

In our study, we have established a novel liquid-driven co-flow focusing (LDCF) process to fabricate curcumin (CUR)-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (CPMs). LDCF-CPMs of size 20.26 ± 2.37 µm have high encapsulation efficiency (>70%) and were intended for application in ovarian cancer by intraperitoneal (IP) administration. LDCF-CPMs have smooth surface with narrow size distribution and a core-shell structured verified by confocal microscopy which can be precisely controlled by changing the flow rates of focusing, outer and inner phases. The LDCF-CPMs reveal the physiochemical stability with sustained release profile corresponding to 95% CUR release over a period of 14 days in an in vitro release medium. Moreover, LDCF-CPMs were testified for cytotoxicity against SKOV-3 ovarian cancer cell lines and peritoneal delivery advantages by animal experiments. The pharmacokinetics of LDCF-CPMs in rats following IP injection shows slow systemic absorption with mean residence time (MRT) of 13.54 h in comparison with 9.82 and 6.74 h for SE-CPMs and free CUR, respectively. In addition, IP delivery of CUR can expose the ovarian tumour to higher concentration for a longer duration by programming the thickness of the shell. The study provides compelling evidence for LDCF-CPMs having high therapeutic opportunity in the treatment of peritoneal cancers, such as ovarian, that reside in the peritoneal cavity.


Assuntos
Antineoplásicos Fitogênicos , Curcumina , Nanopartículas , Neoplasias Ovarianas , Ácido Poliglicólico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Ratos , Ratos Wistar , Ensaios Antitumorais Modelo de Xenoenxerto
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