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2.
Int J Mol Sci ; 15(2): 2761-72, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24552875

RESUMO

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Transplante Heterólogo , Verapamil/química , Verapamil/toxicidade , Vincristina/química , Vincristina/toxicidade
3.
Int J Mol Sci ; 15(3): 3373-88, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24573250

RESUMO

Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a double emulsification method. The processing parameters including the polymer types, organic phase, PVA types and amount were systemically investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock copolymers and lipids, had high entrapment efficiency (65%), submicron size (150 nm) and negatively charged surface (-23 mV). DSC analysis demonstrated the successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs was verified by TEM. Sal released slowly from the LPNPs without apparent burst release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising Sal vehicle for anti-cancer therapy and worthy of further investigation.


Assuntos
Antineoplásicos/química , Glucosídeos/química , Lipídeos/química , Nanopartículas/química , Fenóis/química , Polímeros/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Glucosídeos/farmacologia , Humanos , Microscopia Eletrônica de Transmissão , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Fenóis/farmacologia , Polietilenoglicóis/química , Poliglactina 910/química , Solubilidade , Solventes/química , Água/química
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