IngentaConnect PEGylated nanostructured lipid carriers loaded with 10-hydroxycam...

Authors: Zhang, Xinxin¹; Gan, Yong²; Gan, Li²; Nie, Shufang³; Pan, Weisan⁴

Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 8, August 2008 , pp. 1077-1087(11)

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.

Document Type: Review article

DOI: 10.1211/jpp.60.8.0014

Affiliations: 1: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, P.O. Box 122, Shenyang 110016, PR China, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, 555 Zu-Chong-Zhi Road 2: Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, 555 Zu-Chong-Zhi Road, Shanghai 201203, PR China 3: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, P.O. Box 122, Shenyang 110016, PR China 4: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, P.O. Box 122, Shenyang 110016, PR China., Email: xinxin_8209@hotmail.com

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PEGylated nanostructured lipid carriers loaded with 10-hydroxycamptothecin: an efficient carrier with enhanced anti-tumour effects against lung cancer