New Folate-Grafted Chitosan Derivative To Improve Delivery of Paclitaxel-Loaded Solid Lipid Nanoparticles for Lung Tumor Therapy by Inhalation.
Rémi RosièreMatthias Van WoenselMichel GelbckeVéronique MathieuJulien HecqThomas MathivetMarjorie VermeerschPierre Van AntwerpenKarim AmighiNathalie WauthozPublished in: Molecular pharmaceutics (2018)
Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery systems improve selectivity for cancer cells and tumor penetration and allow sufficient lung residence. To this end, we developed solid lipid nanoparticles (SLN) with modified surface properties. We successfully synthesized a new folate-grafted copolymer of polyethylene glycol (PEG) and chitosan, F-PEG-HTCC, with a PEG-graft ratio of 7% and a molecular weight range of 211-250 kDa. F-PEG-HTCC-coated, paclitaxel-loaded SLN were prepared with an encapsulation efficiency, mean diameter, and zeta potential of about 100%, 250 nm, and +32 mV, respectively. The coated SLN entered folate receptor (FR)-expressing HeLa and M109-HiFR cells in vitro and M109 tumors in vivo after pulmonary delivery. The coated SLN significantly decreased the in vitro half-maximum inhibitory concentrations of paclitaxel in M109-HiFR cells (60 vs 340 nM, respectively). We demonstrated that FR was involved in these improvements, especially in M109-HiFR cells. After pulmonary delivery in vivo, the coated SLN had a favorable pharmacokinetic profile, with pulmonary exposure to paclitaxel prolonged to up to 6 h and limited systemic distribution. Our preclinical findings therefore demonstrated the positive impact of the coated SLN on the delivery of paclitaxel by inhalation.
Keyphrases
- drug delivery
- induced apoptosis
- cell cycle arrest
- sentinel lymph node
- pulmonary hypertension
- cancer therapy
- endoplasmic reticulum stress
- photodynamic therapy
- cell death
- chemotherapy induced
- lymph node
- squamous cell carcinoma
- radiation therapy
- early stage
- wound healing
- cell proliferation
- hyaluronic acid
- cell therapy
- combination therapy
- optic nerve
- rectal cancer