Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis

Zhao, Jinlong; Zhang, Xueyan; Sun, Xiangshi; Zhao, Menghui; Yu, Changhui; Lee, Robert J.; Sun, Fengying; Zhou, Yanmin; Li, Youxin; Teng, Lirong

doi:10.1016/j.ejpb.2018.06.020

Cited by 56 publications

(35 citation statements)

References 23 publications

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“…Slow release at pH 7.4, and faster release at pH 6.0, could be beneficial as it could reduce the amount of the drug in general circulation, thus reducing side effects. In addition, it can concentrate the drug in the acid bacterial infection sites, as acidic pH has been found to be in bacterial infection sites, such as respiratory, intra-abdominal, urinary tract, and skin and soft tissue infections [ 76 , 77 , 78 ]. The release profile during this experiment indicated that VCM release from VCM-loaded StBAclm-Qt 1 quatsomes was pH-responsive and showed potential for application in targeting drugs to diseases that thrive in an acidic environment.…”

Section: Resultsmentioning

confidence: 99%

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

et al. 2020

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Globally, human beings continue to be at high risk of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA); and current treatments are being depleted due to antimicrobial resistance. Therefore, the synthesis and formulation of novel materials is essential for combating antimicrobial resistance. The study aimed to synthesize a quaternary bicephalic surfactant (StBAclm) and thereof to formulate pH-responsive vancomycin (VCM)-loaded quatsomes to enhance the activity of the antibiotic against MRSA. The surfactant structure was confirmed using 1H, 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and high-resolution mass spectrometry (HRMS). The quatsomes were prepared using a sonication/dispersion method and were characterized using various in vitro, in vivo, and in silico techniques. The in vitro cell biocompatibility studies of the surfactant and pH-responsive vancomycin-loaded quatsomes (VCM-StBAclm-Qt1) revealed that they are biosafe. The prepared quatsomes had a mean hydrodynamic diameter (MHD), polydispersity index (PDI), and drug encapsulation efficiency (DEE) of 122.9 ± 3.78 nm, 0.169 ± 0.02 mV, and 52.22 ± 8.4%, respectively, with surface charge switching from negative to positive at pH 7.4 and pH 6.0, respectively. High-resolution transmission electron microscopy (HR-TEM) characterization of the quatsomes showed spherical vesicles with MHD similar to the one obtained from the zeta-sizer. The in vitro drug release of VCM from the quatsomes was faster at pH 6.0 compared to pH 7.4. The minimum inhibitory concentration (MIC) of the drug loaded quatsomes against MRSA was 32-fold and 8-fold lower at pH 6.0 and pH 7.4, respectively, compared to bare VCM, demonstrating the pH-responsiveness of the quatsomes and the enhanced activity of VCM at acidic pH. The drug-loaded quatsomes demonstrated higher electrical conductivity and a decrease in protein and deoxyribonucleic acid (DNA) concentrations as compared to the bare drug. This confirmed greater MRSA membrane damage, compared to treatment with bare VCM. The flow cytometry study showed that the drug-loaded quatsomes had a similar bactericidal killing effect on MRSA despite a lower (8-fold) VCM concentration when compared to the bare VCM. Fluorescence microscopy revealed the ability of the drug-loaded quatsomes to eradicate MRSA biofilms. The in vivo studies in a skin infection mice model showed that groups treated with VCM-loaded quatsomes had a 13-fold decrease in MRSA CFUs when compared to the bare VCM treated groups. This study confirmed the potential of pH-responsive VCM-StBAclm quatsomes as an effective delivery system for targeted delivery and for enhancing the activity of antibiotics.

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Section: Resultsmentioning

confidence: 99%

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

et al. 2020

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“…Therefore, developing highly specific theranostic methods is imperative. In recent years, stimulus-responsive smart systems for targeted imaging and precision therapy of OA have attracted increasing interest, such as pH [4,5], ROS [6] or NO [7] triggered drug release systems upon exposure to inflammation tissues in OA. However, triggering by one stimulus usually suffer from 'false positive' or narrow responsive range in the in vivo microenvironments which are dynamically complex and contain various interfering signals.…”

Section: Introductionmentioning

confidence: 99%

MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Lan

Chen

Pang

et al. 2020

Preprint

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Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA). However, stimulus-responsive therapeutic platform with high specificity for OA basing on the two markers has not been developed yet. We herein demonstrate a new stimuli-responsive theranostic strategy against OA based on a novel multifunctional nano-micelle which is rationally designed and yet readily synthesized. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro an in vivo evidences.

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“…Methotrexate (MTX) has been one of the most commonly applied therapeutic agents in the treatment of lymphomas, breast cancer, choriocarcinoma and lung cancer. MTX is capable to enter cells via a similar transportation system to folic acid (FA), due to the structural similarity of MTX with FA and presence of FA receptor as targeting ligand on the surface of the cancer cells [39,40]. In this study, the polyethylene glycol passivated CD (CDs-PEG) with stronger optical-absorbing ability were synthesized by economical and facile microwave pyrolysis method using gelatin as the carbon source and PEG as the passivator.…”

Section: Introductionmentioning

confidence: 99%

Microwave-assisted and one-step synthesis of PEG passivated fluorescent carbon dots from gelatin as an efficient nanocarrier for methotrexate delivery

Arsalani

Nezhad‐Mokhtari

Jabbari

2019

Artificial Cells, Nanomedicine, and Biotechnology

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A green and simple process for preparing the polyethylene glycol passivated fluorescent carbon dots (CDs-PEG) have been studied by a microwave pyrolysis method, using gelatin and PEG as starting materials. This method is very effective for development of carbon-based quantum dots from gelatin with high quantum yield (QY). The synthesized CDs-PEG were found to emit blue photoluminescence (PL) with a maximum QY of 34%. At the following research, we investigated the effect of the presence of PEG on PL intensity, and the result showed that CDs-PEG becomes stronger PL properties than pure CDs from gelatin. The synthesized CDs-PEG were characterized by FTIR, TEM, UV-vis, PL, zeta potential and XRD analyses. The anticancer performance of developed CDs-PEG was evaluated by in vitro tests such as MTT assay and fluorescence microscopy analyses. The examination of CDs-PEG as an anticancer drug nanocarrier for methotrexate (MTX) illustrated a better antitumor efficacy than free MTX due to its enhanced nuclear delivery in vitro, which resulting in highly effective tumour growth inhibition and improving targeted cancer therapy in clinical medicine.

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Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis

Cited by 56 publications

References 23 publications

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Microwave-assisted and one-step synthesis of PEG passivated fluorescent carbon dots from gelatin as an efficient nanocarrier for methotrexate delivery

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