Polyethylene glycol-complexed cationic liposome for enhanced cellular uptake and anticancer activity

Center for Bioactive Molecular Hybrids and Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
International Journal of Pharmaceutics (Impact Factor: 3.79). 09/2009; 382(1-2):254-61. DOI: 10.1016/j.ijpharm.2009.08.002
Source: PubMed

ABSTRACT Liposomes as one of the efficient drug carriers have some shortcomings such as their relatively short blood circulation time, fast clearance from human body by reticuloendothelial system (RES) and limited intracellular uptake to target cells. In this study, polyethylene glycol (PEG)-complexed cationic liposomes (PCL) were prepared by ionic complex of cationically charged liposomes with carboxylated polyethylene glycol (mPEG-COOH). The cationic liposomes had approximately 98.6+/-1.0 nm of mean particle diameter and 45.5+/-1.1 mV of zeta potential value. While, the PCL had 110.1+/-1.2 nm of mean particle diameter and 18.4+/-0.8 mV of zeta potential value as a result of the ionic complex of mPEG-COOH with cationic liposomes. Loading efficiency of model drug, doxorubicin, into cationic liposomes or PCL was about 96.0+/-0.7%. Results of intracellular uptake evaluated by flow cytometry and fluorescence microscopy studies showed higher intracellular uptake of PCL than that of Doxil. In addition, in vitro cytotoxicity of PCL was comparable to cationic liposomes. In pharmacokinetic study in rats, PCL showed slightly lower plasma level of DOX than that of Doxil. In vivo antitumor activity of DOX-loaded PCL was comparable to that of Doxil against human SKOV-3 ovarian adenocarcinoma xenograft rat model. Consequently, the PCL, of which surface was complexed with PEG by ionic complex may be applicable as drug delivery carriers for increasing therapeutic efficacy of anticancer drugs.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.
    PLoS ONE 09/2014; 9(7):e103736. DOI:10.1371/journal.pone.0103736 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, and the treatment effects are usually unsatisfactory. Vinorelbine (VRB) is extensively used in cancer treatment, but it has some disadvantages when used alone. PEGylated liposomes have been extensively used as a delivery carrier for antitumor drugs via prolonging the circulation time in the blood. Purpose: The nanostructured liposomes were designed and prepared for treating NSCLC. Methods: In the liposomes, PEG was modified on the liposomal surface, DC-Chol was used as cationic materials, and VRB plus quinacrine were encapsulated in an aqueous core of the liposomes as an antitumor drug and an apoptosis-inducing agent, respectively. Evaluations were performed on A549 cells, tubular network formations and xenografts of the A549 cells. Results: The PEGylated drugs-loaded cationic liposomes could significantly enhance cellular uptake and selectively accumulate in A549 cells, thus leading to show strongest antitumor efficacy to tumor cells and to tumor-bearing mice. Action mechanisms showed that the enhanced efficacy in treating NSCLC was related to activate caspase 9 and caspase 3, to activate Bax and P53, and to suppress Bcl-2 and Mcl-1. Conclusion: The PEGylated VRB plus quinacrine cationic liposomes showed a potential strategy for treating NSCLC.
    Journal of Drug Targeting 11/2014; 23(3):1-12. DOI:10.3109/1061186X.2014.979829 · 2.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DMPC and DSPC liposomes were prepared via thin film hydration method followed by sonication. Propranolol solution was incorporated into liposomes at hydration stage. TEM images showed the sizes of DSPC and DMPC were around 88 and 137 nm, respectively. The highest encapsulation ratio of propranolol was approximately 70% using DSPC/CHO/OCT liposomes, which release the drug over 60% in 24 h and reached 100% in 48 h. Both propranolol (10-8-10-6 M) and DSCP liposomes-encapsulated propranolol showed over 1.5-fold increases in the proliferation of human osteoblastic cells hFOB1.19 while differentiation of the cells was approximately doubled by plain and liposomal propranolol, indicating that the stimulatory effects of liposomal propranolol are similar with those of propranolol on human osteoblastic hFOB1.19 cells. The phosphatidylcholine liposomes-encapsulated propranolol prepared in this study potentially possesses anabolic effects in vivo and is also a promising anti-osteoporotic agent in future.
    Bio-medical materials and engineering 01/2014; 24(5):1875-87. DOI:10.3233/BME-140997 · 0.85 Impact Factor