Abstract |
Most drugs do not have the pharmacokinetic features required for optimal pulmonary delivery. In this study, we developed PEGylated nanostructured lipid carriers (PEG-NLCs) to improve the delivery of anti-tumour agents to lung tumours. PEG-40 NLCs modified with PEG-40 stearate (molecular weight 2000 Da), PEG-100 NLCs modified with PEG-100 stearate (molecular weight 5000 Da) and NLCs without PEG modification were prepared by melt-emulsification and homogenization, and were loaded with 10-hydroxycamptothecin ( HCPT). They were investigated in terms of physiological characteristics, biodistribution, cellular uptake, and anti-tumour effect in-vivo. PEG-NLCs exhibited regular morphology, with a spherical shape. The particle size (measured by laser diffraction) was approximately 100 nm. Encapsulation in PEG-NLCs protected the active lactone form of HCPT compared with HCPT solution after incubation with plasma. In biodistribution studies, PEG-NLCs, especially PEG-40 NLCs, had longer circulation time and decreased uptake by the reticuloendothelial system (RES) compared with unmodified NLCs. PEG-NLCs accumulated in the lungs after i.v. injection in mice. PEG-NLCs showed enhanced cellular uptake by human lung adenocarcinoma epithelial A549 cells. In-vivo experiments indicated that PEG-NLCs loaded with HCPT have superior efficacy against A549 lung cancer compared with HCPT solution and NLCs. These results suggest that PEG-NLCs is a promising delivery system for HCPT in the treatment of lung cancer.
|
Authors | Xinxin Zhang, Yong Gan, Li Gan, Shufang Nie, Weisan Pan |
Journal | The Journal of pharmacy and pharmacology
(J Pharm Pharmacol)
Vol. 60
Issue 8
Pg. 1077-87
(Aug 2008)
ISSN: 0022-3573 [Print] England |
PMID | 18644200
(Publication Type: Journal Article)
|
Chemical References |
- Antineoplastic Agents, Phytogenic
- Drug Carriers
- Stearates
- Polyethylene Glycols
- 10-hydroxycamptothecin
- Camptothecin
|
Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(chemistry, pharmacokinetics, pharmacology)
- Camptothecin
(analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
- Cell Line, Tumor
- Chemistry, Pharmaceutical
- Drug Carriers
- Drug Compounding
- Drug Stability
- Female
- Humans
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Molecular Weight
- Nanostructures
- Particle Size
- Polyethylene Glycols
(chemistry)
- Solubility
- Stearates
(chemistry)
- Tissue Distribution
|