title: PEGylated nanostructured lipid carriers loaded with 10-hydroxycamptothecin: an efficient carrier with enhanced anti-tumour effects against lung cancer.
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.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, P.O. Box 122, Shenyang 110016, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.forename: Shufang
authors.initials: S
authors.lastname: Nie
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008970:Molecular Weight; D049329:Nanostructures; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013228:Stearates / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D013228:Stearates; D011092:Polyethylene Glycols; C028098:10-hydroxycamptothecin; D002166:Camptothecin