A Gastric Cancer Peptide GX1-Modified Nano-Lipid Carriers Encapsulating Paclitaxel: Design and Evaluation of Anti-Tumor Activity.

The aim of this study was to develop a GX1-modified nanostructured lipid carrier (NLCs) and to evaluate its ability to improve the anti-gastric cancer tumor effects of paclitaxel (PTX). The GX1-modified NLCs were synthesized and loaded with PTX (GX1-PTX-NLCs) by emulsion solvent evaporation technique. The anti-tumor activity and pharmacodynamics were then evaluated by in vitro cell studies and animal experiments. The GX1-modified NLCs were successfully synthesized and confirmed by 1H NMR and MALDI-TOF-MS. PTX-loaded NLCs produced particles with average size distribution less than or equal to 222 nm and good drug loading and entrapment efficiency. In vitro studies demonstrated that GX1-PTX-NLCs had a more obvious inhibitory effect on Co-HUVEC cells than PTX and unmodified PTX-NLCs. The cellular uptake results also showed that GX1-PTX-NLCs were largely concentrated in Co-HUVEC cells, and the uptake rates of GX1-PTX-NLCs in Co-HUVEC were higher than those of the free drug and the PTX-NLC. In vivo studies demonstrated that GX1-PTX-NLCs possess strong anti-tumor effect and showed higher tumor growth inhibition and lower toxicity in nude mice. These results suggest that GX1-modified NLCs enhanced the anti-tumor activity of PTX and reduced its toxicity effectively. GX1-PTX-NLCs may be considered as a potent drug delivery system for therapy of gastric cancer.

Jian Y ，Zhao M ，Cao J ，Fan T ，Bu W ，Yang Y ，Li W ，Zhang W ，Qiao Y ，Wang J ，Wen A ... -  《Drug Design Development and Therapy》

Targeted Nanostructured Lipid Carriers for Delivery of Paclitaxel to Cancer Cells: Preparation, Characterization, and Cell Toxicity.

Low water solubility, high systemic toxicity and insignificant cellular uptake have limited efficient clinical applications of the anti-tumor agent Paclitaxel (PTX). To overcome these limitations, a Novel Nanostructured Lipid Carrier (NLC) modified with Folic Acid (FA) and polyethylene glycol (PEG) was prepared by emulsion solvent evaporation method using cholesterol, α-tocopherol, lecithin and Poloxamer. A partial factorial design was applied to determine the appropriate levels of variables for optimized formulation. Formulations were evaluated for Particle Size (PS), Zeta Potential (ZP), Entrapment Efficiency (EE), and release efficiency (RE72%). FA- and PEGconjugated octadecylamine (FA-ODA and PEG-ODA) were synthesized and confirmed by FTIR and H-NMR and incorporated either alone or in combination with the optimized formulation whose properties were also evaluated. PTX-loaded optimized, targeted, pegylated, targeted/pegylated NLCs, pure PTX, and Anzatax® along with their respective controls were selected for toxicity evaluation on human breast cancer cell line, MCF-7, using MTT assay. PS, ZP, EE%, and RE72% of the optimized formulation were 154.6 nm, -16.5 mv, 79.1% and 49.3%, respectively. Incorporation of α-tocopherol as the liquid lipid allowed for more efficient drug encapsulation, PS reduction, enhanced stability and sustained-release of the drug. Cytotoxicity of PTX-loaded NLCs modified with both FA-ODA and PEG-ODA was significantly enhanced compared to that of free PTX and other drug-loaded modified NLCs. The results suggest that preparation of NLCs with synthesized conjugates might be a promising candidate for drug delivery of PTX to the cancerous cells and has a great potential as a carrier for tumor targeting in breast cancer.

Rezazadeh M ，Emami J ，Hassanzadeh F ，Sadeghi H ，Rostami M ，Mohammadkhani H ... -  《-》

iRGD Co-Administration with Paclitaxel-Loaded PLGA Nanoparticles Enhance Targeting and Antitumor Effect in Colorectal Cancer Treatment.

To explore the targeting effect of PLGA-NP and iRGD co-administration with PTXPLGA NP (PTX-PLGA + iRGD) on colorectal cancer. Whether PLGA-NP co-administration with iRGD peptide could show effective tumor-targeting ability in contrast to with PLGA-NP in colorectal cancer mice models was evaluated. Moreover, the chemotherapeutics Paclitaxel (PTX) was loaded into the PLGA-NP to impart anti-tumor efficiency to the PTX-PLGA. Whether iRGD co-administration with PTX-PLGA NP (PTX-PLGA + iRGD) in colorectal cancer models enabled PTX to achieve better anti-tumor efficiency and biocompatibility was further assessed. The targeting ability of PLGA-NP was enhanced in cell experiment and colorectal cancer mice models by co-administration of iRGD. As a result, PTX-PLGA + iRGD achieved better anti-tumor efficacy than PTX and PTX-PLGA. Conlusion: The nanocarrier based on PLGA with specific targeting ability could promote the clinical application of various chemotherapeutics similar to PTX. The combination of drug-loaded nanoparticles and iRGD could develop into a promising drug delivery system.

Li L ，Yang M ，Li R ，Hu J ，Yu L ，Qian X ... -  《-》

Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design.

Emami J ，Rezazadeh M ，Sadeghi H ，Khadivar K ... -  《-》

Synergistic combination therapy of lung cancer: Cetuximab functionalized nanostructured lipid carriers for the co-delivery of paclitaxel and 5-Demethylnobiletin.

Lung cancer remains the leading cause of cancer associated deaths worldwide. Recent efforts have been focused on combinational and nanoparticulate therapies that can efficiently deliver multiple therapeutics. Herein, we reported cetuximab (CET) functionalized, paclitaxel (PTX) and 5-Demethylnobiletin (DMN) co-loaded nanostructured lipid carriers (NLCs) (CET-PTX/DMN-NLCs). The morphology, particle size, zeta potential, stability and drug release were tested. Cellular uptake, cell viability, synergistic effects and in vivo anti-tumor effects were evaluated on human lung adenocarcinoma cells (A549 cells), human embryonic lung cells (MRC-5 cells) and A549 paclitaxel-resistant cells bearing mice models. NLCs had sizes of around 130 nm and zeta potentials of +20-30 mV. The release of drugs from NLCs was relatively fast at the first 12 h and then became slow until completion of sustained release behavior. Cells uptake of CET-PTX/DMN-NLCs (65.8%) was remarkably higher than that of PTX/DMN-NLCs (35.5%) in A549 cells. The combination treatment with PTX and DMN synergistically decreases the viability of cells than the single PTX-NLCs and DMN-NLCs. CET-PTX/DMN-NLCs exhibited the most remarkable in vivo tumor inhibition efficiency, which suspended the tumor growth from 1010.23 to 211.18 mm3 at the end of the study. The highest tumor accumulation amount and low toxicity made CET-PTX/DMN-NLCs a promising system for the synergistic combination therapy of lung cancer.

Guo S ，Zhang Y ，Wu Z ，Zhang L ，He D ，Li X ，Wang Z ... -  《-》