Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 104
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomaterials ; 311: 122678, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38917705

RESUMO

Drug transmission through the blood-brain barrier (BBB) is considered an arduous challenge for brain injury treatment following the return of spontaneous circulation after cardiac arrest (CA-ROSC). Inspired by the propensity of melanoma metastasis to the brain, B16F10 cell membranes are camouflaged on 2-methoxyestradiol (2ME2)-loaded reactive oxygen species (ROS)-triggered "Padlock" nanoparticles that are constructed by phenylboronic acid pinacol esters conjugated D-a-tocopheryl polyethylene glycol succinate (TPGS-PBAP). The biomimetic nanoparticles (BM@TP/2ME2) can be internalized, mainly mediated by the mutual recognition and interaction between CD44v6 expressed on B16F10 cell membranes and hyaluronic acid on cerebral vascular endothelial cells, and they responsively release 2ME2 by the oxidative stress microenvironment. Notably, BM@TP/2ME2 can scavenge excessive ROS to reestablish redox balance, reverse neuroinflammation, and restore autophagic flux in damaged neurons, eventually exerting a remarkable neuroprotective effect after CA-ROSC in vitro and in vivo. This biomimetic drug delivery system is a novel and promising strategy for the treatment of cerebral ischemia-reperfusion injury after CA-ROSC.

2.
Food Chem ; 447: 138971, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38461718

RESUMO

This study introduces an innovative approach for the valorization and protection of anthocyanins from 'Benihoppe' strawberry (Fragaria × ananassa Duch.) based on acidified natural deep eutectic solvent (NADES). Choline chloride-citric acid (ChCl-CA, 1:1) was selected and acidified to enhance the valorization and protection of anthocyanins through hydrogen bond. The optimal conditions (ultrasonic power of 318 W, extraction temperature of 61 °C, liquid-to-solid ratio of 33 mL/g, ultrasonic time of 19 min), yielded the highest anthocyanins of 1428.34 µg CGE/g DW. UPLC-Triple-TOF/MS identified six anthocyanins in acidified ChCl-CA extract. Stability tests indicated that acidified ChCl-CA significantly increased storage stability of anthocyanins in high temperature and light treatments. Molecular dynamics results showed that acidified ChCl-CA system possessed a larger diffusion coefficient (0.05 m2/s), hydrogen bond number (145) and hydrogen bond lifetime (4.38 ps) with a reduced intermolecular interaction energy (-1329.74 kcal/mol), thereby efficiently valorizing and protecting anthocyanins from strawberries.


Assuntos
Antocianinas , Fragaria , Solventes/química , Antocianinas/química , Fragaria/química , Solventes Eutéticos Profundos , Extratos Vegetais/química
3.
Biomedicines ; 12(2)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38398021

RESUMO

In clinical practice, drug therapy for cancer is still limited by its inefficiency and high toxicity. For precision therapy, various drug delivery systems, including polymeric micelles self-assembled from amphiphilic polymeric materials, have been developed to achieve tumor-targeting drug delivery. Considering the characteristics of the pathophysiological environment at the drug target site, the design, synthesis, or modification of environmentally responsive polymeric materials has become a crucial strategy for drug-targeted delivery. In comparison to the normal physiological environment, tumors possess a unique microenvironment, characterized by a low pH, high reactive oxygen species concentration, hypoxia, and distinct enzyme systems, providing various stimuli for the environmentally responsive design of polymeric micelles. Polymeric micelles with tumor microenvironment (TME)-responsive characteristics have shown significant improvement in precision therapy for cancer treatment. This review mainly outlines the most promising strategies available for exploiting the tumor microenvironment to construct internal stimulus-responsive drug delivery micelles that target tumors and achieve enhanced antitumor efficacy. In addition, the prospects of TME-responsive polymeric micelles for gene therapy and immunotherapy, the most popular current cancer treatments, are also discussed. TME-responsive drug delivery via polymeric micelles will be an efficient and robust approach for developing clinical cancer therapies in the future.

4.
Small ; 20(3): e2303916, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37705134

RESUMO

The induction of anti-drug antibody (ADA) is a formidable challenge for protein-based therapy. Trichosanthin (TCS) as a class of ribosome-inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co-administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self-assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co-injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti-TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin-based anticancer therapy and for promoting the clinical translation.


Assuntos
Nanopartículas , Tricosantina , Humanos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Formação de Anticorpos , Tricosantina/farmacologia , Tricosantina/uso terapêutico , Anticorpos , Polietilenoglicóis
5.
Nanoscale Horiz ; 8(7): 870-886, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-36987679

RESUMO

Targeted co-delivery and co-release of multi-drugs is essential to have an integrative collaborative effect on treating cancer. It is valuable to use few drug carriers for multi-drug delivery. Herein, we develop cRGD-modified nanoparticles (cRGD-TDA) of a conjugate of doxorubicin as cytotoxic agent, adjudin as an anti-metastasis agent and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a reactive oxygen species inducer linked with pH-sensitive bonds, and then combine the nanoparticles with PD-L1 antagonist to treat 4T1 triple-negative breast cancer. cRGD-TDA NPs present tumor-targeted co-delivery and pH-sensitive co-release of triple agents. cRGD-TDA NPs combined with PD-L1 antagonist much more significantly inhibit tumor growth and metastasis than single-drug treatment, which is due to their integrative collaborative effect. It is found that TPGS elicits a powerful immunogenic cell death effect. Meanwhile, PD-L1 antagonist mitigates the immunosuppressive environment and has a synergistic effect with the cRGD-TDA NPs. The study provides a new strategy to treat refractory cancer integratively and collaboratively.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antígeno B7-H1 , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Nanopartículas/química , Concentração de Íons de Hidrogênio
6.
Acta Biomater ; 154: 123-134, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36306985

RESUMO

Clinically, colorectal stents can only palliatively relieve obstruction caused by colorectal cancer (CRC), with a high incidence of stent migration and tumor-related re-obstruction. To overcome these shortcomings, we developed a colorectal stent composed of a structure-optimized nitinol braided stent and a tubular film including an inner layer of poly (ethylene-co-vinyl acetate) (EVA) and a segmental outer layer of EVA with paclitaxel (PTX). The braiding pattern, segment number, and end shape of the stent were optimized based on the mechanical properties, ex vivo and in vivo anti-migration performance, and tissue response of the stent. The optimized nitinol stent had a structure of one middle segment in a hook-pattern and two end segments in a cross-pattern with two studs on each end in a staggered arrangement. Structure-optimized colorectal stents were prepared and evaluated in vivo. PTX released from the stent was mostly distributed in the rabbit rectum in contact with it. The biosafety of the colorectal stent was evaluated using blood tests, biochemical analysis, anatomical observation, and pathological analysis. The anti-tumor effect of the stent was also evaluated by endoscopy, anatomical observation, and pathological and immunohistochemical analyses in rabbits with orthotopic CRC. The results demonstrate that the optimized colorectal stents have effective anti-migration ability and anti-tumor effects with good biosafety. STATEMENT OF SIGNIFICANCE: In order to overcome the most common disadvantages of migration and re-obstruction of colorectal stents clinically, a colorectal stent composed of a structure-optimized nitinol stent and a tubular film including an inner layer of EVA and a segmental outer layer of EVA with PTX was put forward in this study. The optimized nitinol stent had a structure of one middle segment in hook-pattern and two end segments in cross-pattern with two studs on each end in staggered arrangement. The resulting colorectal stent has been proved with good anti-migration ability, anti-tumor effects, and biosafety in vivo, which provides a safe and effective potential treatment modality for patients with colorectal cancer.


Assuntos
Ligas , Neoplasias Colorretais , Animais , Coelhos , Ligas/farmacologia , Ligas/química , Stents , Paclitaxel
7.
Int J Biol Macromol ; 193(Pt A): 768-777, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34717982

RESUMO

It is well known that metal ions have great effects on gelling behaviors of gellan aqueous systems, however, the effects of their co-ions - anions have rarely been studied. Herein, we investigated the effects of four kinds of sodium salts with different anions (NaCl, CH3COONa, Na2C2O4 and Na3C6H5O7) on gelling behaviors of gellan aqueous systems in terms of gelling temperature and gel hardness. It was found that, when [Na+] was low (20 mM), the salt with Cl- or CH3COO- favored the gelling of gellan aqueous systems, while the salt with C2O42- or C6H5O73- took adverse effects probably because C2O42- or C6H5O73- could react with divalent cations (Ca2+ and Mg2+) in gellan to form precipitates or chelates and break their interactions with gellan (salt bridges). When [Na+] was high (50 or 80 mM), all the four kinds of salts facilitated gelling due to the shielding effects of high concentrations of Na+ on the negative charges along the gellan chains, and followed the order of: Cl- > CH3COO- > C2O42- > C6H5O73-. This study demonstrates the effects of anion kind of salts on gelling behaviors of gellan aqueous systems and provides references for the application of gellan.


Assuntos
Géis/química , Íons/química , Polissacarídeos Bacterianos/química , Sais/química , Sódio , Temperatura , Água
9.
Int J Pharm ; 606: 120869, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34245845

RESUMO

Excessive growth of tumor within biliary wall and formation of biofilm on inner surface of stent can cause restenosis or even obstruction after stent implantation. Therefore, it is important and valuable to develop a new biliary stent for anti-cholangiocarcinoma and anti-biofilm formation. Herein, we designed, prepared and primarily evaluated a new trilayered film for biliary stents consisting of one poly (lactic acid) (PLA) layer loaded with anti-tumor paclitaxel (PTX layer), one middle PLA isolation layer (isolation layer) and one PLA layer loaded with antimicrobial ofloxacin (OFLX layer). It is postulated that the PTX layer releases drug towards biliary wall with tumor, the OFLX layer releases drug towards lumen of bile duct and the isolation layer is used to separate from the PTX layer and the OFLX layer and facilitate drug release in unidirectional way. The prepared trilayered films were characterized in terms of morphology, microstructure, crystallinity and biodegradability. It was found that the films could effectively tune drug release by addition of different amounts of drug or PEG, release PTX and OFLX in opposite directions, effectively inhibit the proliferation of human cholangiocarcinoma RBE cells, the adherence of E. coli and S. aureus and the formation of biofilm in vitro. It is potential that the trilayered films can be used to fabricate a new biliary stent with a dual function of anti-cholangiocarcinoma and anti-biofilm formation.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Stents Farmacológicos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Escherichia coli , Humanos , Paclitaxel , Staphylococcus aureus , Stents
10.
Curr Drug Targets ; 22(8): 870-881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390113

RESUMO

Generally, poor solubility and imprecise delivery of chemotherapeutic drugs can compromise their efficacies for clinical cancer treatment. In order to address such concerns, poor water-soluble drugs are conjugated with poly(ethylene glycol) (PEG) to obtain PEGylated drugs, which have improved water solubility and can also self-assemble in an aqueous solution to form micelles (PEGylated drug micelles). The surface PEG layer enhances the micelles' colloidal stability and reduces the interaction with physiological surroundings. Meanwhile, PEGylated drug micelles are tumor- targeting via the enhanced permeation and retention (EPR) effect to improve antitumor efficacy in comparison with free drugs. PEGylated drug micelles employ drugs as parts of the carrier medium, which increases the micelles' drug loading capacity relatively. The development of stimuli- responsive PEGylated drug micelles facilitates the drug release to be smart and controllable. Moreover, the PEGylated drug micelles show great potentials in overcoming the challenges of cancer therapy, such as multidrug resistance (MDR), angiogenesis, immunosuppression, and so on. In this review, we highlight the research progresses of PEGylated drug micelles, including the structures and properties, smart stimuli-responsive PEGylated drug micelles, and the challenges that have been overcome by PEGylated drug micelles.


Assuntos
Portadores de Fármacos , Micelas , Neoplasias , Polietilenoglicóis , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Solubilidade
11.
Int J Biol Macromol ; 159: 659-666, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32439451

RESUMO

The moisture sorption and desorption properties of hard capsules have a great influence on the quality of capsule products. However, studies on them have rarely been reported. Herein, we studied the moisture sorption and desorption properties of three kinds of hard capsules (gelatin, hydroxypropyl methyl cellulose (HPMC) and pullulan capsules) in terms of hygroscopicity, crystallinity, thermal behaviors and so on. It is found that HPMC capsules have weaker moisture sorption ability and moisture keeping ability than pullulan or gelatin capsules with lower moisture sorption rates, equilibrium moisture contents, moisture keeping rates and higher critical relative humidity. In comparison with gelatin capsules, pullulan capsules have weaker moisture sorption ability and comparable moisture keeping ability. HPMC or pullulan capsules can more effectively protect high, moderate and low hygroscopic capsule contents (chitosan, potato starch or ethyl cellulose) from outside moisture absorption. The diffraction peaks of the moisture equilibrated gelatin, HPMC and pullulan capsules are much smaller than those of their dried ones. The dried and the moisture equilibrated gelatin, HPMC or pullulan capsules all have smooth surface morphology. HPMC or pullulan capsules can be an attractive alternative to animal gelatin capsules due to their appropriate moisture sorption and desorption properties.


Assuntos
Cápsulas/química , Gelatina/química , Glucanos/química , Derivados da Hipromelose/química , Água/análise , Varredura Diferencial de Calorimetria , Cápsulas/análise , Quitosana/química , Gelatina/análise , Glucanos/análise , Derivados da Hipromelose/análise , Amido/química , Propriedades de Superfície , Difração de Raios X
12.
Carbohydr Polym ; 238: 116190, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32299551

RESUMO

κ-Carrageenan (κ-Ca) is often used to facilitate gelling of aqueous solutions of polysaccharides. However, studies on its effects on pullulan's rheological and texture properties and pullulan (PUL) hard capsule performances have rarely been reported. Herein, effects of κ-Ca on PUL solutions, hydrogels, films and hard capsules were investigated. It was found that the gelling temperature of 15 % (w/w) PUL solutions with 0.07 % KCl increased from 34 ℃ to 42 ℃ as the concentration of κ-Ca increased from 0.6 % to 1.2 %, and the gelling temperature rose from 25 ℃ to 37 ℃ by adding a small amount of KCl (0.07 %) for 15 % PUL solutions with 0.9 % κ-Ca. As the κ-Ca concentration increased, hardness, fracturability and adhesiveness rose for PUL gels and tensile stress increased for PUL films. PUL capsules could be easily prepared by the aid of κ-Ca, and performances of capsules could be adjusted by changing the amount of κ-Ca.

13.
Int J Biol Macromol ; 152: 948-956, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759023

RESUMO

To overcome the different extra-/intracellular barriers in gene delivery, tumor-targeted and pH/redox-responsive ternary polyplexes with charge-conversional properties were prepared through a modular self-assembly strategy. Firstly, the thiolated trimethylated chitosan (TMC-SH) was synthesized to crosslink and condense pDNA through electrostatic interaction and disulfide formation, which obtained the TMC-SS/pDNA binary polyplexes with redox-responsive gene release. To further endow the binary polyplexes with tumor targeting and endo/lysosomal pH-triggered charge-reversal properties, a folate conjugated cis-aconitic amide-polyethylenimine (FA-PEI-AcO) was synthesized to shield the positive TMC-SS/pDNA, generating the FA-PEI-AcO/TMC-SS/pDNA ternary polyplexes with a size of ~190 nm and negative surface-charges. The ζ-potential of the polyplexes was stable at physiological pH and increased rapidly from -14 mV to + 20 mV at pH 5.5 (endo/lysosomal pH) due to the breakages of acid-liable amide bonds and the subsequent de-shielding of FA-PEI-AcO layers, which might benefit the endo/lysosomal escape of the polyplexes. Afterward, the polyplexes could redox-responsively release gene at higher intracellular concentrations of glutathione. By taking advantage of such multi-responses, significantly enhanced transfection efficiency was achieved in vitro in Hela cells for the ternary polyplexes. These results suggested that the newly developed polyplexes had potential application for gene delivery.


Assuntos
Quitosana/química , DNA/química , Portadores de Fármacos/química , Ácido Fólico/química , Plasmídeos/genética , Polietilenoimina/química , Compostos de Sulfidrila/química , DNA/genética , Portadores de Fármacos/metabolismo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Metilação , Transfecção
14.
J Mater Chem B ; 7(11): 1951-1961, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255058

RESUMO

Implant infection is one of the most severe complications after orthopedic surgery. The construction of an antibacterial coating on orthopedic implants with release-killing or contact-killing is one of the most efficient strategies to prevent implant-related infections. Here we reported a hydroxypropyltrimethyl ammonium chloride chitosan (HACC) based multilayer modified plasma-sprayed porous titanium coating generated via the layer-by-layer covalent-immobilized method. We demonstrated that the multilayer coating inhibited the colonization and biofilm formation of several bacterial strains, including Staphylococcus aureus (ATCC 25923), methicillin-resistant Staphylococcus aureus (MSRA, ATCC 43300) and clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE 287), in vitro. HACC in the multilayer was released slowly with the degradation of the coating under the action of collagenase, further killing the planktonic bacteria, while the remaining HACC could kill the colonized bacteria. In a rat model of femur implants, the HACC-based multilayer-modified TCs effectively controlled the infection caused by MRSA and prevented bone destruction. Therefore, the HACC-based multilayer modified TCs with multiple antimicrobial properties could be a new potential ideal surface modification strategy to prevent implant associated infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Implantes Experimentais/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Células Cultivadas , Quitosana/análogos & derivados , Quitosana/farmacologia , Feminino , Humanos , Ácido Hialurônico/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Ratos , Ratos Sprague-Dawley , Staphylococcus epidermidis/efeitos dos fármacos , Titânio/farmacologia
15.
J Mater Chem B ; 7(6): 974-985, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32255102

RESUMO

To prevent premature drug release from nanoparticles, it is vital to design and prepare controlled and site-specific drug release systems. We investigated a new controllable drug release mesoporous carbon nanoparticle (MCN)-based nano-system with the advantages of enhanced permeability and retention effect (EPR) to target tumors followed by the NIR-induced heat-triggered release of a chemotherapeutic drug to show anti-tumor effects. The pores of MCN with photo-thermal effects were filled with the chemotherapeutic agent doxorubicin (DOX) and the phase change material (PCM) 1-tetradecanol was used as a gatekeeper to trap DOX inside the pores of the mesoporous carbon nanoparticles and the release of DOX inside tumor cells was triggered using NIR irradiation. The surface of MCN was coated with natural sophorolipid (SLPD) to obtain nanoparticles (DOX-PCM@MCN-SLPD) with good biocompatibility, dispersibility and stability in aqueous solutions. The MCN-based nano-system had the ability to load 24% DOX trapped with the PCM before coating with SLPD. It was observed that the release of DOX was temperature-dependent above the melting point of PCM. Once DOXPCM@MCN-SLPD was delivered into MCF-7/ADR cells, the release of DOX was triggered by MCN-borne photo-thermal effects under NIR irradiation. The amount of DOX inside the tumor was visualized via confocal laser scanning microscopy, which showed a higher amount of DOX at a higher temperature compared to that at normal body temperature, further confirming the minimization of premature drug release at 37 °C.


Assuntos
Carbono/química , Doxorrubicina/metabolismo , Raios Infravermelhos , Nanopartículas/química , Ácidos Oleicos/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Hipertermia Induzida , Células MCF-7 , Tamanho da Partícula , Porosidade , Espécies Reativas de Oxigênio/metabolismo
16.
Int J Biol Macromol ; 126: 37-43, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30584939

RESUMO

Gelatinization is an important property of starch for biomedical applications. However, studies on the changes in starch granules in terms of morphology, swelling, amylose leaching and so on during gelatinization, which are key to uncovering the starch gelatinization process, have rarely been reported. Herein, changes of cassava and potato starch granules during gelatinization were investigated. It was found that there is a substantial difference in the granule changes during gelatinization between cassava and potato starch. Cassava starch granules remain intact with slight swelling, with approximately 8.5% amylose leaching in water for 30 min at 60 °C. In sharp contrast, potato starch granules swell very well and rapidly, losing much integrity with 51.05% amylose leaching. The gelatinization time and temperature have much greater effects on the changes of potato starch granules than cassava starch granules.


Assuntos
Fenômenos Químicos , Manihot/química , Solanum tuberosum/química , Amido/química , Amilopectina/química , Amilose/química , Varredura Diferencial de Calorimetria , Peso Molecular , Amido/ultraestrutura
17.
Int J Pharm ; 553(1-2): 510-521, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30308274

RESUMO

Paclitaxel (PTX), one of the most potent anticancer agents, has showed a remarkable activity against varieties of tumors. However, the bioavailability of PTX is quite low due to its poor aqueous solubility. Moreover, the emerging multidrug resistance (MDR) in cancer to PTX remains a major obstacle for successful chemotherapy. In order to address these problems, we developed self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) (Biotin-PEG-PCDA) for PTX delivery (termed as PTX-BPC NPs) with the application of mPEG2K-P(CL-co-LLA) as an emulsifier. The loading content and encapsulation efficiency of PTX were 13.2% and 92.0%, respectively. In vitro drug release study showed that PTX-BPC NPs could degrade rapidly and then release the PTX payload in a 10 mM glutathione (GSH) environment. Compared with free PTX, PTX-BPC NPs exhibited enhanced anticancer efficacy (IC50(MCF-7/ADR cells), 17.28 µg/mL vs. 1.15 µg/mL). In addition, these biotin-modified nanoparticles could also significantly reverse PTX resistance by suppressing the over-expression of P-gp, thus resulting in increased intracellular drug accumulation and reduced drug efflux in MCF-7/ADR cells, which showed a great anticancer effect.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Nanopartículas , Paclitaxel/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Biotinilação , Neoplasias da Mama/patologia , Química Farmacêutica/métodos , Curcumina/administração & dosagem , Curcumina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Excipientes/química , Glutationa/metabolismo , Humanos , Concentração Inibidora 50 , Células MCF-7 , Paclitaxel/química , Paclitaxel/farmacologia , Polietilenoglicóis/química , Solubilidade
18.
Int J Pharm ; 552(1-2): 91-98, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30244147

RESUMO

Intratumoral implants have aroused great interests for local chemotherapy of cancer, however, how to efficiently control drug release from implants is still a great challenge. Herein, we designed and prepared a new hollow bullet-shaped implant with porous surface by 3D printing, loaded chemotherapeutic agent cytoxan (CTX) with tetradecyl alcohol or lecithin as matrix and coated it with poly (lactic acid) to obtain a CTX implant, which has a highly tuned drug release property with a drug release time from 4 h to more than 1 month. The drug release from the implant can be easily controlled by changing pore sizes, kinds of matrices, and coating thickness.


Assuntos
Antineoplásicos Alquilantes/química , Ciclofosfamida/química , Implantes de Medicamento , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Lecitinas/química , Poliésteres/química , Porosidade , Impressão Tridimensional
19.
Int J Pharm ; 553(1-2): 29-36, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30267754

RESUMO

Anti-tumor drug/stent combinations play a dual role of stent and local chemotherapy to cancer. Herein, a series of paclitaxel (PTX) loaded polylactic acid (PLA) stent films were studied on drug release characteristics and in vivo antitumor effects. The film was implanted beneath and released drug towards the subcutaneous PC-3 tumor xenograft in mice, which consisted of a PTX-loaded layer and a drug-free backing layer. The concentrations of PTX were 103-104 times higher than those in normal 20 tissue or organs in 26 days after implantation of the 50% PTX/20% PEG-loaded film, indicating an extreme accumulation of PTX in tumor tissue. The tumor volumes kept unchanged for the initial 10 days after implantation of the PTX-loaded films and then increased slightly, implying tumor growth was remarkably inhibited. Moreover, the results showed that the drug release can be effectively modulated by addition of PEG in the drug-loaded layer, present an unidirectional way by adding a backing layer, and the drug films could arrest PC-3 prostate cancer cells in G2/M phase and induce apoptosis after 300 days of drug release. With the advantages of prolonged drug release and long-term effectiveness, the films have great potential for anti-tumor treatment by local administration.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Stents Farmacológicos , Paclitaxel/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/farmacologia , Poliésteres/química , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Control Release ; 288: 126-135, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30194946

RESUMO

Despite advances in cancer therapy, metastasis remains the dominate reason for cancer-related mortality. Herein, a novel, hybrid nanocomplex, RDG/shRNA, with tumor-targeting and dual stimuli responsive properties is described for the effective treatment of metastatic cancer. This multimodal therapeutic system was prepared by complexing RDG nanovectors with p65-shRNA, an anti-NF-κB agent, via the electrostatic interactions between negatively charged shRNA and the cationic DSPEI displayed on the surface of the nanovectors. Cytosolic release of shRNA from the complex is achieved by dual-stimulation from NIR laser irradiation and high intracellular GSH concentrations, resulting in effective gene silencing of metastatic 4T1 breast cancer cells, thereby inhibiting cell proliferation and invasion. More importantly, the nanocomplex undergoes significant intratumoral accumulation due to the EPR effect and RGD-mediated endocytosis. In combination with localized NIR laser irradiation, the hybrid complex could effectively inhibit primary breast tumor growth and almost completely suppresses distant metastasis, significantly improving the therapeutic efficacy of the RDG/shRNA complex. Consequently, this NIR-light and GSH responsive complex with tumor targeting capabilities and cytosolic shRNA release is a promising nanoplatform for precise treatment of metastatic cancer.


Assuntos
Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Citosol , Portadores de Fármacos/administração & dosagem , Feminino , Glutationa/metabolismo , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia , Polietilenoglicóis/administração & dosagem , Polietilenoimina/administração & dosagem , Polietilenoimina/análogos & derivados , RNA Interferente Pequeno/efeitos da radiação , Fator de Transcrição RelA/genética , Carga Tumoral/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...