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 ... -  《-》

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 ... -  《-》

Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment.

Raikwar S ，Vyas S ，Sharma R ，Mody N ，Dubey S ，Vyas SP ... -  《AAPS PHARMSCITECH》

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》

Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo.

Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer prodrug because of its poor antitumor efficiency. But surprisingly, it was found in our study that PEG-PTX could form a novel nanoparticle system with free PTX. To address how this system works, we compared PTX loaded PEG-PTX nanoparticles (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection available (Taxol(®)) in vitro and in vivo. Firstly, it was found that PEG-PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX crystal formation and drug release. Then it was demonstrated that coumarin loaded PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG-PLA micelles and solvent system of Taxol(®). In the efficacy study with MCF-7 tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity than PEG-PLA/PTX at the same PTX dosage. At the dose of 10mg free PTX per kg, PEG-PTX/PTX displayed similar efficacy as Taxol(®) but less toxicity evaluated by the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX showed significantly better efficacy than Taxol(®). In conclusion, with favorable characteristics in stability, cellular uptake, cytotoxicity, biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a nanocarrier for PTX delivery.

Lu J ，Chuan X ，Zhang H ，Dai W ，Wang X ，Wang X ，Zhang Q ... -  《-》