Preparation and evaluation of 2-methoxyestradiol-loaded pH-sensitive liposomes

The development and clinical application of 2-methoxyestradiol (2-ME) as a new type of antitumor drug are limited due to its poor solubility, rapid metabolism in vivo, and large oral dosage. 2-ME-loaded pH-sensitive liposomes (2-ME-PSLs) was prepared containing the lipids, Lipoid E-80 (E-80), cholesteryl hemisuccinate (CHEMS), and cholesterol (CHOL) via thin-film ultrasonic dispersion. First, preparation conditions of 2-ME-PSLs were optimized by orthogonal test. Then 2-ME-PSL was characterized, and the release behavior and stability of 2-ME-PSL in vitro were evaluated. The optimal preparation conditions for 2-ME-PSLs were as follows: 2-ME : E-80+CHEMS 1:15; CHOL : E-80+CHEMS 1:5; ultrasonication time 20 minutes. The mean particle size, PDI, zeta potential, and entrapment efficiency (EE) of 2-ME-PSLs were 116 ± 9 nm, 0.161 ± 0.025, −22.4 ± 1.7 mV, and 98.6 ± 0.5%, respectively. As viewed under a transmission electron microscope, 2-ME-PSLs were well dispersed and almost spherical. They exhibited significant pH-sensitive properties and were fairly stable when diluted with a physiological solution. In conclusion, 2-ME-PSLs were successfully prepared and possessed a favorable pH sensitivity and good dissolution stability with a normal solution

Liver targeting anti-tumor activity of pH-sensitive liposomes loaded with lactosyl-norcantharitin phospholipids complex / 中草药

Objective: To investigate the antitumor activity of pH-sensitive liposomes (pH-LPC-lips) loaded with lactosyl-norcantharitin (Lac-NCTD) phospholipids complex in vitro and in vivo, and the liver targeting in mice. Methods: Using blank liposomes (blank-lips and blank-pH-lips) as control, the MTT assay was used to study the cytotoxic effects of Lac-NCTD and its liposomes (Lac-lips and pH-LPC-lips) on human hepatoma carcinoma cells HepG2. HPLC assay was used to evaluate the uptake of Lac-NCTD and its liposomes in HepG2. In vivo antitumor activity of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The hepatocyte specificity of near-infrared fluorescence dye (Cy7)-labeled pH-LPC-lips in H22 tumor-bearing mice was monitored through NIR fluorescence real-time tumor imaging instrument. Results: The pH-LPC-lips demonstrated stronger cytotoxicity against tumor cells HepG2 and easily permeated the cell membrane, compared with Lac-NCTD and Lac-lips. The results of antitumor activity in vivo showed that pH-LPC-lips displayed best tumor inhibitory effect. The optical imaging results indicated that Cy7-labeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice, which could reduced the side effect, and increased the antitumor activity. Conclusion: The pH-LPC-lips could take the initiative to release at the tumor site and showed the liver-targeting. As a result, the preparation could be regarded as novel liver-targeting agent which has better antitumor effect.

Technetium-99m-labeled stealth pH-sensitive liposomes: a new strategy to identify infection in experimental model

The diagnosis of inflammatory and infectious processes is an important goal in medicine. The use of radiopharmaceuticals for identification of inflammation and infection foci has received considerable attention. The aim of this work was to evaluate the uptake and the imaging potential of stealth pH-sensitive liposomes radiolabelled with 99mTechnetium (99mTc) to identify infection sites in mice. The liposomes containing glutathione were labeled with 99mTc-Hexamethylpropyleneamine oxime (HMPAO) complex. The 99mTc-labeled stealth pH-sensitive liposomes (99mTc-SpHL) were injected in mice bearing infection in the right thigh muscle induced by Staphylococcus aureus. Biodistribution studies and scintigraphic imaging were performed at different times after injection of radiopharmaceutical. The 99mTc-SpHL was significantly uptaken by abscess when compared to the respective control. The abscess was visualized as early as 0.5 hours after injection of 99mTc-SpHL becoming more prominent with the time. These results indicate that 99mTc-SpHL is a promising radiopharmaceutical for visualizing infection foci in patients.

O diagnóstico de processos inflamatórios e infecciosos é um objetivo importante em medicina. O uso de radiofármacos para identificação de focos de inflamação e infecção tem recebido considerável atenção. O objetivo deste trabalho foi avaliar a captação e o potencial de imagem de lipossomas pH-sensíveis furtivos radiomarcados com 99mTecnécio (99mTc) para identificar sítios de infecção em camundongos. Os lipossomas contendo glutationa foram marcados com o complexo 99mTc-hexametilpropilenoamina oxima (HMPAO). Os lipossomas pH-sensíveis furtivos marcados com 99mTc (99mTc-LpHS) foram injetados em camundongos com infecção induzida por Staphylococcus aureus no músculo da coxa direita. Estudos de biodistribuição e imagem cintilográfica foram realizados em diferentes tempos após injeção do radiofármaco. Os 99mTc-LpHS foram captados significativamente pelo abscesso quando comparado ao respectivo controle. O abscesso foi visualizado rapidamente (0,5 horas) após injeção do 99mTc-LpHS tornando-se mais evidenciado com o tempo. Estes resultados indicam que 99mTc-LpHS é um promissor radiofármaco para identificação de focos inflamatórios e infecciosos em pacientes.