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Development of pH-Sensitive Cationic PEGylated Solid Lipid Nanoparticles for Selective Cancer-Targeted Therapy.
- Source :
-
Journal of biomedical nanotechnology [J Biomed Nanotechnol] 2017 Feb; Vol. 13 (2), pp. 192-03. - Publication Year :
- 2017
-
Abstract
- Solid lipid nanoparticles (SLNs) are suitable candidates for the delivery of various anti-cancer drugs. However, currently insufficient tumor-permeability and non-specific uptake by the reticuloendothelial system limits the application of SLNs. Here, we developed novel pH-sensitive cationic polyoxyethylene (PEGylated) SLNs (PEG-SLNs+) that could accumulate long-term at various tumor sites to enhance the therapeutic efficiency of camptothecin (CPT). These CPT-loaded PEG-SLNs+ (CPT-PEG-SLNs+) were spherical nanoparticles, with small size (∼52.3±1.7 nm), positive charge (∼34.3±3.5 mV) and high entrapment efficiency (∼99.4±1.7%). Drug release profile indicated the overall released amount of CPT from CPT-PEG-SLNs+ at pH 5.5 was 20.2% more than at pH 7.4, suggesting CPT-PEG-SLNs+ were a pH-sensitive SLNs. This PEG-SLNs+ could be efficiently uptaken into cells to inhibit the proliferation of CL1-5 cells (IC50 = 0.37 ±0.21 ug/ml) or HCC36 cells (IC50 = 0.16±0.43 ug/ml). In living animal, our PEG-SLNs+ could accumulate long-term (for more than 120 hours) in various types of tumor, including human lung carcinoma (NCI-H358, CRL5802, CL1-5), human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HCC36), and CPT-PEG-SLNs+ could efficiently enhance the therapeutic efficiency of CPT to suppress the growth of the HCC36 or CL1-5 tumors. Therefore, Successful development of these pH-sensitive PEGylated cationic SLNs may provide a selective and efficient drug delivery system for cancer therapy.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Camptothecin chemistry
Camptothecin pharmacokinetics
Camptothecin pharmacology
Cell Line, Tumor
Drug Delivery Systems
Humans
Lipids chemistry
Mice
Mice, Nude
Particle Size
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacokinetics
Rats
Rats, Sprague-Dawley
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Camptothecin analogs & derivatives
Cell Proliferation drug effects
Lipids pharmacology
Nanoparticles chemistry
Polyethylene Glycols pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-7033
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of biomedical nanotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 29377649
- Full Text :
- https://doi.org/10.1166/jbn.2017.2338