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1.
Acta Biomater ; 105: 1-14, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001369

RESUMO

The translocation of natural cell membranes to the surface of synthetic nanoparticles, which allows man-made vectors to share merits and functionalities created by nature, has been a hot subject of research in the past decade. The resulting biomimetic nanoparticles not only retain the physicochemical properties of nanomaterials, but also inherit the advantageous functions of source cells. Combined with the preponderances of both synthetic and natural platforms, the optimized biomimetic systems can maximize the drug delivery efficiency. In this review, we first summarize the preparation strategies of the biomimetic systems from the perspective of the correlation between the properties of nanoparticles and cell membranes. Six types of cell membrane-camouflaged nanoparticles are further introduced with an emphasis on their properties and performance. Finally, a concluding remark regarding the primary challenges and opportunities associated with these nanoparticles is presented. STATEMENT OF SIGNIFICANCE: Translocation of natural cell membranes to the surface of synthetic nanoparticles has been repeatedly highlighted in the past decade to endow man-made vectors with merits and functionalities created by nature; therefore, the resulting biomimetic systems not only retain the physicochemical properties of nanomaterials but also inherit the biological functions of source cells for efficient drug delivery. To provide a timely review on this hot and rapidly developing subject of research, this paper summarized recent progress on the cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy, and focused primarily on six different types of cell membrane-coated nanoparticles with an emphasis on the preparation strategies from the perspective of the correlation between the properties of nanoparticles and cell membrane.

2.
ACS Appl Mater Interfaces ; 11(11): 10578-10588, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30802029

RESUMO

Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.


Assuntos
Materiais Biocompatíveis/química , MicroRNAs/metabolismo , Pró-Fármacos/química , Proteína ADAM17/metabolismo , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular , Quitosana/química , Regulação para Baixo/efeitos dos fármacos , Portadores de Fármacos/química , Sinergismo Farmacológico , Fluoruracila/química , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/química , Nanopartículas/química , Nanopartículas/toxicidade , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
3.
Artif Cells Nanomed Biotechnol ; 46(sup3): S661-S670, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30307317

RESUMO

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas , Nanopartículas , Pectinas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Pectinas/química , Pectinas/farmacocinética , Pectinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Drug Deliv ; 24(1): 459-466, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28219253

RESUMO

A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quitosana/análogos & derivados , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Fluoruracila/análogos & derivados , Fluoruracila/administração & dosagem , Nanopartículas/química , Pró-Fármacos/administração & dosagem , Células A549 , Absorção Fisiológica , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quitosana/efeitos adversos , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Glicosilação , Meia-Vida , Hemólise/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Coelhos , Distribuição Aleatória , Ratos Sprague-Dawley , Distribuição Tecidual
5.
J Drug Target ; 24(2): 169-77, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26211366

RESUMO

BACKGROUND: Human pancreatic carcinoids, a type of neuroendocrine tumors, are asymptomatic and difficult to diagnose, with the effects of traditional anti-cancer therapies being limited. The histone deacetylase (HDAC) inhibitor valproic acid (VPA) was evaluated for its effects alone and in combination with receptor-targeting peptide-drug conjugate via increasing drug internalization. MATERIALS AND METHODS: The in vitro and in vivo assays were used to evaluate the effects of VPA and somatostatin receptor-targeting camptothecin-somatostatin conjugate (CPT-SST). RESULTS: VPA induced proliferation suppression, cell apoptosis and cell cycle arrest. VPA acts as a HDAC inhibitor to induce a decrease of HDAC4 and an increase of acetylated histone 4 (AcH4). Meanwhile, most importantly, besides activating Notch signaling, VPA was observed to stimulate the expression of somatostatin receptor type 2 (SSTR2) that has been applied for receptor-targeting therapies. This characteristic was used for a combination therapy of VPA and CPT-SST. The combination displayed much more potent anti-tumor effects on carcinoid tumor growth by increasing SSTR2 density and drug internalization in target tumor cells. CONCLUSION: The combination of VPA and a SSTR2-targeting agent provides us a promising approach in treatment of carcinoid tumors.


Assuntos
Proliferação de Células/efeitos dos fármacos , Peptídeos/metabolismo , Receptores de Peptídeos/metabolismo , Receptores de Somatostatina/metabolismo , Ácido Valproico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Camundongos , Camundongos Nus , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Receptores Notch/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Curr Top Med Chem ; 16(3): 281-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26126914

RESUMO

Self-assembled peptide nanomaterials display the advantageous properties of injectability, biodegradability and biocompatibility. These peptide nanomaterials, by self-assembling, can be widely applied in such fields as drug delivery (small molecules and large molecules), regenerative medicine and nanobiotechnology. In this review, we mainly discuss the properties of these peptide nanomaterials in their physical, chemical and biological aspects. Also discussed are recent advances in their potential applications as drug delivery systems and for uses in regenerative medicine. These current advances show a bright future for the development and clinical applications of self-assembled peptide-based nanotechnology and nanomedicine. However, there are still some big challenges for us to face before these peptide nanomaterials eventually can be used for the treatment of human diseases.


Assuntos
Nanomedicina , Nanoestruturas/química , Peptídeos/química , Medicina Regenerativa , Animais , Sistemas de Liberação de Medicamentos , Humanos , Peptídeos/síntese química
7.
Curr Pharm Des ; 22(4): 506-13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26517529

RESUMO

The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the hydrophobicity of free DOX. This work proposes a novel strategy for in-situ one-step synthesis of macromolecular pro-drugs and fabrication of a core-shell micelle, demonstrating great potential for cancer chemotherapy.


Assuntos
Doxorrubicina/síntese química , Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Micelas , Pectinas/síntese química , Pró-Fármacos/síntese química , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Química Farmacêutica , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Feminino , Células Hep G2 , Humanos , Substâncias Macromoleculares/síntese química , Masculino , Nanopartículas , Pectinas/farmacologia , Pró-Fármacos/farmacologia , Coelhos
8.
9.
Curr Top Med Chem ; 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26395318
10.
J Cancer ; 6(10): 996-1004, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26366213

RESUMO

Hepatocellular carcinoma (HCC) is a type of malignant cancer. Notch signaling is aberrantly expressed in HCC tissues with more evidence showing that this signaling plays a critical role in HCCs. In the present study, we investigate the effects of the anti-convulsant drug valproic acid (VPA) in HCC cells and its involvement in modulating Notch signaling. We found that VPA, acting as a histone deacetylase (HDAC) inhibitor, induced a decrease in HDAC4 and an increase in acetylated histone 4 (AcH4) and suppressed HCC cell growth. VPA also induced down-regulation of Notch signaling via suppressing the expression of Notch1 and its target gene HES1, with an increase of tumor suppressor p21 and p63. Furthermore, Notch1 activation via overexpressing Notch1 active form ICN1 induced HCC cell proliferation and anti-apoptosis, indicating Notch signaling played an oncogenic role in HCC cells. Meanwhile, VPA could reverse Notch1-induced increase of cell proliferation. Interestingly, VPA was also observed to stimulate the expression of G protein-coupled somatostatin receptor type 2 (SSTR2) that has been used in receptor-targeting therapies. This discovery supports a combination therapy of VPA with the SSTR2-targeting agents. Our in vitro assay did show that the combination of VPA and the peptide-drug conjugate camptothecin-somatostatin (CPT-SST) displayed more potent anti-proliferative effects on HCC cells than did each alone. VPA may be a potential drug candidate in the development of anti-HCC drugs via targeting Notch signaling, especially in combination with receptor-targeting cytotoxic agents.

12.
Biomater Sci ; 3(7): 1050-60, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26221939

RESUMO

Cyclodextrins (CDs) represent the most extensively investigated cyclic molecules due to their wide availability, facile functionalization, unique amphiphilicity and inclusion capacity. The marriage of CD chemistry with polymer science has generated novel biomaterials by integrating supermolecular host-guest chemistry and state-of-the-art polymer chemistry techniques. The current mini-review focuses on the recent progress in CD-functionalized polymers as drug carriers for cancer therapy. CD-functionalized polymers with different structures are summarized. Their application as drug carriers for cancer therapy is then highlighted. In the end, the future directions of this rapidly developing research field are discussed.


Assuntos
Ciclodextrinas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/terapia , Polímeros/química , Humanos
13.
Curr Top Med Chem ; 16(2): 133-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26126910

RESUMO

Multiple Gαi protein-coupled somatostatin receptors (SSTRs) are expressed in human kidney and liver tissues. Also, aberrant cAMP signaling has been shown to play a critical role in cysto-genesis and enlargement of the human kidney and liver. Thus, somatostatin (SST) analogs become potential and promising alternatives in treating human polycystic kidney disease (PKD) and polycystic liver disease (PLD) via interacting with Gαi protein-coupled SSTRs and further blocking cAMP production. Lanreotide is a synthetic, long-acting SST analog with high binding affinity to SSTR2, and has been clinically approved for the treatment of acromegaly due to excessive growth hormone. Recently, this SST analog has been applied in the treatment of PKD and PLD, and has shown an effective reduction of liver and kidney volume compared to placebo. This review will discuss the discovery of this peptide and its clinical applications in the treatment of PKD/PLD patients.


Assuntos
Cistos/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Doenças Renais Policísticas/tratamento farmacológico , Somatostatina/análogos & derivados , Humanos , Peptídeos Cíclicos/química , Somatostatina/química , Somatostatina/uso terapêutico
14.
Mol Pharm ; 11(2): 638-44, 2014 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-24383625

RESUMO

The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/uso terapêutico , Pectinas/farmacologia , Pectinas/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Bioensaio , Cápsulas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração Inibidora 50 , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Tamanho da Partícula , Pectinas/química , Ratos
15.
J Microencapsul ; 27(2): 171-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19538029

RESUMO

Microparticle protein delivery systems based on calcium alginate were fabricated using a very convenient method, i.e. directly shredding the protein-loaded calcium alginate beads into microparticles in a commercial food processor for 3 min. Bovine serum albumin (BSA) as a model protein was encapsulated in the calcium alginate microparticles. The obtained protein-loaded microparticles were then coated with chitosan. This fabrication method offered high encapsulation efficiency and a high particle yield. Compared with beads, the microparticles exhibited a faster release rate in the initial release stage. By comparing the release profiles of uncoated beads/microparticles and chitosan-coated beads/microparticles, it was found that the releases from chitosan-coated beads/microparticles were slower. To examine whether the loaded protein denatured during the microparticle fabrication, trypsin was encapsulated in the calcium alginate microparticles and the bioactivity of trypsin released from the microparticles was measured.


Assuntos
Alginatos/química , Preparações de Ação Retardada/química , Composição de Medicamentos/métodos , Soroalbumina Bovina/administração & dosagem , Animais , Bovinos , Quitosana/química , Composição de Medicamentos/economia , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Tamanho da Partícula
16.
J Phys Chem B ; 113(45): 14839-43, 2009 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19831369

RESUMO

The effect of the presence of ions on the aggregation behavior of natural polymer alginate in aqueous media was investigated. Through self-assembly of alginate in aqueous solutions containing Ca2+ and CO(3)(2-) ions under very mild conditions, nanosized aggregates with four different morphologies, i.e., nanosphere, vesicle, nanoparticle, and nanorod, could be obtained under different ion concentrations. This study provides a simple approach to prepare organic/inorganic (O/I) hybrid natural polymer based aggregates with different morphologies.


Assuntos
Alginatos/química , Íons/química , Polímeros/química , Alginatos/síntese química , Cálcio , Carbonatos , Ácido Glucurônico/síntese química , Ácido Glucurônico/química , Ácidos Hexurônicos/síntese química , Ácidos Hexurônicos/química , Nanopartículas , Polímeros/síntese química , Soluções
17.
Langmuir ; 25(19): 11720-6, 2009 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-19719161

RESUMO

A novel strategy was developed to prepare nanospheres and vesicles as drug carriers. The drug-loaded pectin nanospheres and vesicles were fabricated in aqueous media containing Ca2+ and CO3(2-) ions under very mild conditions, which did not involve any surfactant. Through adjusting the preparation conditions, nanosized drug delivery systems with diverse morphologies, that is, nanospheres and vesicles, could be obtained. This technique could offer good control over the morphology and the size of nanospheres and vesicles. The morphologies of the aggregates were observed by environmental scanning electron microscopy and transmission electron microscopy. 5-Fluorouracil (5-FU), an antineoplastic drug, was encapsulated in the nanospheres and vesicles, and the in vitro drug release at different pH values was investigated. With the presence of Ca2+ and CO3(2-) ions in the pectin-based nanospheres/vesicles, the release of the low molecular weight drug could be effectively sustained from the highly hydrolyzed polysaccharide-based drug delivery systems.


Assuntos
Portadores de Fármacos/química , Nanosferas/química , Pectinas/química , Cálcio/química , Carbonatos/química , Fluoruracila/química , Fluoruracila/metabolismo , Concentração de Íons de Hidrogênio , Água/química
18.
Colloids Surf B Biointerfaces ; 68(2): 245-9, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19058952

RESUMO

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200mum were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.


Assuntos
Alginatos/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Nanocompostos/química , Nanopartículas/química , Pectinas/química , Soroalbumina Bovina/farmacologia , Animais , Bovinos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Poligalacturonase/farmacologia
19.
Chem Commun (Camb) ; (38): 4598-600, 2008 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-18815696

RESUMO

An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide).


Assuntos
Micelas , Temperatura , Reagentes para Ligações Cruzadas/química , Hidrólise , Polietilenoglicóis/química , Dióxido de Silício/química , Fatores de Tempo , Compostos de Trimetilsilil/química
20.
Int J Pharm ; 357(1-2): 15-21, 2008 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-18313867

RESUMO

Alginate based microparticle drug delivery systems were prepared for the sustained release of antineoplastic drugs. Two drugs, 5-fluorouracil (5-FU) and tegafur, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions, i.e., directly shredding the drug loaded beads into microparticles in a commercial food processor. The mean sizes of the obtained microparticles were between 100 and 200 microm. To effectively sustain the drug release, alginate microparticles were reinforced by chitosan during gelation. The drug release from the chitosan-reinforced alginate microparticles was obviously slower than that from the unreinforced microparticles. The effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified. The effects of drug feeding concentration and pH value of the release medium on the drug release were investigated.


Assuntos
Alginatos/química , Antineoplásicos/administração & dosagem , Quitosana/química , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Antineoplásicos/química , Fenômenos Químicos , Físico-Química , Preparações de Ação Retardada , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Excipientes , Fluoruracila/administração & dosagem , Fluoruracila/química , Microscopia Eletrônica de Varredura , Nanopartículas , Tamanho da Partícula , Polissacarídeos/química , Tegafur/administração & dosagem , Tegafur/química
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