RESUMO
In the current study, the polyurethane acrylate (PUA) polymer was synthesized by the addition reaction between an isophorone diisocyanate (IPDI) and 2-hydroxyethyl acrylate and cured by polyol. Different properties of the synthesized PUA were determined through diverse analysis methods. The polyurethane acrylate (PUA)/natural filler-based composite (rhizome water extract of Costus speciosus) was prepared as an antifouling agent. The results revealed that the lowest weight loss percentages were detected at 2 wt% PUA/natural filler composite loadings with Escherichia coli (ATCC 23,282) and Pseudomonas aeruginosa (ATCC 10,145). The decreased weight loss percentage may be attributed to the well dispersed natural composite resulting in a slippery surface that can prevent fouling adhesion. It was concluded that the PUA/natural filler composite might be considered an eco-friendly and economical solution to the biofouling problem. KEY POINTS: ⢠A novel strategy for anti-biofouling. ⢠A new composite reduced Gram-negative bacteria.
Assuntos
Incrustação Biológica , Acrilatos , Incrustação Biológica/prevenção & controle , Escherichia coli , Poliuretanos , Pseudomonas aeruginosaRESUMO
Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid-coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g-1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer.
Assuntos
Dasatinibe/química , Dasatinibe/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lactoferrina/química , Magnetismo/métodos , Micelas , Polímeros/química , Zeína/químicaRESUMO
Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Reagentes de Ligações Cruzadas/química , Feminino , Flavanonas/administração & dosagem , Flavanonas/uso terapêutico , Glutaral/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lactoferrina/química , Células MCF-7 , Micelas , Scutellaria/química , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Zeína/químicaRESUMO
Despite several reports have revealed the beneficial effect of co-administration of COX-2 inhibitors with aromatase inhibitors in managing postmenopausal breast cancer; no nanocarriers for such combined delivery have been developed till now. Therefore, protamine nanocapsules (PMN-NCs) have been developed to co-deliver letrozole (LTZ) that inhibits aromatase-mediated estrogen biosynthesis and celecoxib (CXB) that synergistically inhibits aromatase expression. Inspired by the CD44-mediated tumor targeting ability of hyaluronate (HA), we developed HA-coated PMN-NCs (HA-NCs) via electrostatic layer-by-layer assembly. Moreover, multi-compartmental PEGylated phospholipid-CXB complex bilayer enveloping PMN-NCs (PEG-NCs) were designed for conferring biphasic CXB release from the phospholipid corona and oily core as well as enabling passive-targeting. The NCs demonstrated excellent stability, prolonged circulation and could be scaled up with the aid of spray-drying technology. Hemolysis, serum stability and cytotoxicity studies confirmed the superiority of combined LTZ-CXB nano-delivery. Mechanistically, the NCs especially HA-NCs and PEG-NCs demonstrated precious anti-tumor effects in vivo revealed as reduction in the tumor volume and aromatase level, increased apoptosis, as well as inhibition of VEGF, NF-κB and TNF-α augmented by histopathological and immunohistochemical studies. Overall, our approach provided for the first time a potential strategy for targeted LTZ-CXB combined therapy of hormone-dependent breast cancer via singular nanocapsule delivery system.
Assuntos
Inibidores da Aromatase/farmacologia , Neoplasias da Mama/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Nanocápsulas/química , Protaminas/química , Animais , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα. CONCLUSIONS: Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.