2 research outputs found
Preparation, characterization and <i>in vitro</i> evaluation of microemulsion of raloxifene hydrochloride
<p>Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which is orally used for treatment of osteoporosis and prevention of breast cancer. The drug has low aqueous solubility and bioavailability. The aim of the present study is to formulate and characterize oil-in-water microemulsion systems for oral delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug solvent oil and surfactant, respectively. In the first and second formulations, Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo-ternary phase diagrams showed that the best surfactant/co-surfactant ratios in the first and second formulations were 4:1 and 9:1, respectively. The particle size of all free drug-loaded and drug loaded samples were in the range of 31.25 ± 0.3 nm and 60.9 ± 0.1 nm, respectively. Electrical conductivity coefficient and refractive index of all microemulsion samples confirmed the formation of oil-in-water type of microemulsion. <i>In vitro</i> drug release profile showed that after 24 hours, 46% and 63% of the drug released through the first formulation in 0.1% (w/v) Tween 80 in distilled water as a release medium and phosphate buffer solution (PBS) at pH = 5.5, respectively. These values were changed to 57% and 98% for the second formulation. Results confirmed that the proposed microemulsion system containing RLX could improve and control the drug release profile in comparison to conventional dosage form.</p
Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice
This study reports on the activity
of thermosensitive liposomes (TSLs) incorporating different HSPC ratios
in DPPC/MSPC/PEG<sub>2000</sub>-DSPE matrix (90/10/4) plus mild hyperthermia
(HT) (42 °C). TSLs were loaded with a poorly membrane permeable
anticancer drug, cisplatin, through the passive equilibration method.
The addition of HSPC to the corresponding DPPC lipid matrix increased
the transition temperature. <i>In vitro</i> data demonstrated
>90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within
10 min at 42 °C, while other TSLs bearing HSPC showed greater
stability. The plasma kinetics of cisplatin demonstrated higher cisplatin
leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL)
compared to other formulations. Indeed, increasing HSPC fraction in
liposome bilayers significantly improved drug retention in blood.
Though DPPC 90-LTSL plus one-step HT was expected to provide a unique
drug release, the premature drug leakage as well as the likely wash-back
of a great portion of drug into the blood circulation resulted in
reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC
10/PEG<sub>2000</sub>-DSPE 4 liposomes plus two-step HT greatly enhanced
the survival of animals. In particular, the improved delivery of cisplatin
through stabilized DPPC 30/HSPC 60/MSPC 10/PEG<sub>2000</sub>-DSPE
4 liposomes in two-step mild HT enhanced antitumor efficacy compared
to other formulations. Thus, prolonged exposure of cancer cells to
cisplatin through stabilized liposomes would be an efficient approach
in improving the survival of animals