The antitumor activities of the structurally-similar two-species aromatics Tonalide and Pearlide and the enhancement of their effects by hyperthermia.

Antitumor activities have been reported for the aromatics Tonalide (6-acetyl-1,1,2,4,4,7-hexamethyl-tetrahydronaphthalene, AHTN) and Pearlide (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-γ-2-benzopyran, HHCB), which are contained in detergents. In this study, their carcinostatic activities in Ehrlich ascites tumor (EAT) cells were evaluated by mitochondrial dehydroganase-based WST-1 assay and dye-exclusion assay. The viability of EAT cells treated at 37 or 42°C for 30 min and sequentially cultured at 37°C was assayed at graded times. Immediately after treatment at 37°C, neither Tonalide nor Pearlide had an effect on EAT cells, even at a concentration as high as 200 µM. However, cell viability was reduced to 40% versus the control after 20 h of culture with Tonalide at 50 µM, and to below 20% at 25 µM after 72 h. In contrast, Pearlide was nearly inactive, even at a dose of 100 µM after 20 h of culture, and only reduced cell viability to 41.2% after 72 h. After treatment at 42°C without culture, neither of the aromatics was effective, even at a dose of 200 µM. The viability of cells cultured with Tonalide for 20 h after treatment at 42°C was reduced to nearly half of that at 37°C, and to 10% of the control after culture for 72 h. These values for the reduction of cell viability were also acheived by the Trypan blue dye-exclusion assay. The lifespan-prolonging effects of Tonalide on mice implanted with EAT cells were also examined. The lifespan of mice administrated 1.8 mg/day of Tonalide was prolonged by up to 28 days, while mice that did not receive Tonalide died within a mean of 15 days. Thus, Tonalide exhibited marked carcinostatic effects in vitro and in vivo and may prove to be a potent multipurpose antitumor agent in combination with hyperthermia.

Evaluation of the permeability of hair growing ingredient encapsulated PLGA nanospheres to hair follicles and their hair growing effects.

This paper describes the process of encapsulating hair growing ingredients in the PLGA nanospheres by emulsion solvent diffusion method and investigates the feasibility of using the PLGA nanospheres as the DDS (Drug delivery System) carriers for delivering various hair growing ingredients to hair follicles. In-vitro and in-vivo tests were conducted to verify the performances of encapsulated PLGA nanospheres with three different hair growing ingredients. In the in-vitro tests, the scalp-pore permeability of hair growing ingredient encapsulated PLGA nanospheres (dispersed in the PBS solution) was examined using human scalp biopsies in a modified Bronaugh diffusion chamber in comparison to that of the control samples containing the hair growing ingredient in the PBS solution. Furthermore, the hair growing effect of the encapsulated PLGA nanospheres was evaluated with the C3H mice in the in-vivo tests. By observing the fluorescence intensity of the ingredients, as shown in the cross-section photographs of the human scalp biopsies, it was found that the dispersion liquids containing hair growing ingredient encapsulated PLGA nanospheres exerted a scalp-pore permeability 2.0- to 2.5-fold more marked than that of the control samples. Also, the hair growing activities were enhanced by using the encapsulated PLGA nanospheres, which transformed the hair growth cycle from the resting phase to the growing phase. As a result, the degree of hair growth was improved significantly. These results suggested that the PLGA nanosphere can be a new DDS carrier for delivering hair growing ingredients and drugs to the hair follicles.

The effect of poly (aspartic acid-co-lactic acid) nanospheres on the lung metastasis of B16BL6 melanoma cells by intravenous administration.

Poly (aspartic acid-co-lactic acid) (PAL) has been investigated as a new biodegradable material for Drug Delivery Systems (DDS). Similar to the poly (lactic acid-co-glycolic acid) (PLGA) nanospheres, the PAL nanospheres can control-release encapsulated drugs by hydrolysis and adhere to the mucous membranes to improve the drug absorption. In this study, the vitamin encapsulated PAL nanospheres were applied on mice to examine their effect on tumor metastasis and safety as an injectable DDS material for anti-cancer and other drugs. In the experiment, 6 C57BL/6 mice per group were intravenously administered with B16BL6 melanoma cells (1 x 10(5) per mouse) and non-encapsulated PAL nanospheres or pro-vitamin encapsulated nanospheres respectively, while the control group was administered with B16BL6 cells alone. Two weeks later, the lungs of the mice were excised and metastatic foci on the lung surface were counted. The melanoma cell metastasis to lungs was prevented by intravenous co-injection of B16BL6 melanoma cells with 1.7 microg of pro-vitamin E encapsulated PAL nanospheres. Its metastatic foci count (mean +/- SD) was 127+/-80, which was better than the control (246+/-95, p<0.02). Also, applying the pro-vitamin C and pro-vitamin A encapsulated PAL nanospheres as well as the non-encapsulated PAL nanospheres slightly decreased the number of metastasis colonies in the lungs as compared to that of the control. These results suggested that PAL nanospheres did not promote the lung metastasis of B16BL6 melanoma cells. Thus, the PAL nanospheres are safe material for injection applications.