Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged liposome-entrapped methotrexate to rats

Journal of Microencapsulation
C K Kim, J H Han

Abstract

The lymph node targeting ability and pharmacokinetics of methotrexate (MTX) after intramuscular (i.m.) injection of differently charged liposome-entrapped [3H]MTX to rats were evaluated using [3H]MTX as a tracer. Neutral liposomes were prepared with a mixture of phosphatidylcholine, cholesterol and alpha-tocopherol (8:4:0.1, molar ratio). Positively and negatively charged liposomes were also prepared by incorporation of stearylamine (8:4:0.1, molar ratio) and dicetylphosphate (8:4:0.1:1, molar ratio) into neutral liposomes respectively. The encapsulation efficiency (as expressed in terms of radioactivity) in liposomes was increased as alpha-tocopherol was incorporated into the lipid bilayer. The disappearance of [3H]MTX from the i.m. injection site was rapid and essentially complete after 30 min. On the other hand, the disappearance of radioactivity of liposome-entrapped [3H]MTX was much slower when compared to free drug. The area under the drug concentration-time curve (AUC) of liposome-entrapped [3H]MTX in lymph nodes was significantly increased when compared to free [3H]MTX. It suggested that liposomes injected by the i.m. route entered into the lymphatics and only drug released from liposomes diffused directly into the syst...Continue Reading

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Citations

Jul 24, 2002·Archives of Pharmacal Research·Chong-Kook Kim, Soo-Jeong Lim
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