Ceramide and N,N,N-Trimethylphytosphingosine-Iodide (TMP-I)-Based Lipid Nanoparticles for Cancer Therapy

Autor: Alexander Jahn, Prabagar Balakrishnan, Hyun-Jong Cho, Chung Kil Song
Rok vydání: 2015
Předmět:
Zdroj: Pharmaceutical Research. 33:206-216
ISSN: 1573-904X
0724-8741
DOI: 10.1007/s11095-015-1780-5
Popis: To evaluate the anti-tumor effect of ceramide or trimethylphytosphingosine-iodide (TMP-I) containing solid lipid nanoparticles (SLNs) prepared using trymyristin, phosphatidylcholine (PC), and Pluronic P85 (P85) for intravenous delivery of docetaxel.Docetaxel-loaded SLNs using ceramide or TMP-I at 3.22% (w/w) with a mean diameter of 89-137 nm were successfully prepared by high pressure homogenization. The prepared nanoparticles were characterized by particle size, zeta potential, drug content, and TEM analysis. Cellular uptake and cytotoxicity were studied using adriamycin-resistant breast cancer (MCF-7/ADR) cells. The optimized formulation's dissolution profile, pharmacokinetics, and antitumor effect in mice tumor model were compared with that of control (Taxotere(®)).The drug release rate of docetaxel from SLNs was lower than that of control (Taxotere(®)). The prepared SLNs showed higher cellular uptake of docetaxel compared to that of Taxotere(®) in MCF-7/ADR cell lines, which was further confirmed by the confocal laser scanning microscopy (CLSM) study using coumarin 6 (C6). Prepared SLNs exhibited significantly increased antitumor efficacy, compared to Taxotere(®), in MCF-7/ADR cells. In vivo pharmacokinetic study in rats (at 10 mg/kg dose) showed that the SLNs significantly reduced in vivo clearance of drug than Taxotere(®). Interestingly, ceramide and TMP-I SLNs efficiently inhibited the tumor growth compared to Taxotere(®) in MCF-7/ADR tumor xenografted mouse model.This work showed that TMP-I and ceramide SLNs not only significantly enhanced systemic exposure of drug, but also increased antitumor efficacy compared to Taxotere(®) and control SLN.
Databáze: OpenAIRE
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