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In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion.

Zhang YT, Huang ZB, Zhang SJ, Zhao JH, Wang Z, Liu Y, Feng NP - Int J Nanomedicine (2012)

Bottom Line: Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions.Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle.The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai, The People's Republic of China.

ABSTRACT

Objective: To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures.

Materials and methods: A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity.

Results: The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed.

Conclusion: The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

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Influence of microemulsion concentration on cellular morphology.
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f7-ijn-7-2465: Influence of microemulsion concentration on cellular morphology.

Mentions: In comparison with normal cellular morphology (Figure 7), it was found that microemulsion administration did not lead to transformation of the cellular morphology. Furthermore, the cellular morphology did not obviously transform with an increase in the microemulsion concentration. Pharmaceutical adjuncts of the prepared microemulsion, such as PEG-400 (11.2%, w/w)39 and Cremophor EL (33.8%, w/w), are used extensively in the pharmaceutical industry. Cremophor EL use has been reported, up to the 50% level, as a solubilizer in preparations of paclitaxel injections,40 and when used in this study, no obvious transformation of cellular morphology was observed with an inverted microscope. Ethyl oleate is extensively used in topical medications and is designated by the US Food and Drug Administration as harmless, which is supported by the results of a 91-day feeding study in rats.41 This evidence supports the finding that the microemulsion has little cellular toxicity.


In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion.

Zhang YT, Huang ZB, Zhang SJ, Zhao JH, Wang Z, Liu Y, Feng NP - Int J Nanomedicine (2012)

Influence of microemulsion concentration on cellular morphology.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367489&req=5

f7-ijn-7-2465: Influence of microemulsion concentration on cellular morphology.
Mentions: In comparison with normal cellular morphology (Figure 7), it was found that microemulsion administration did not lead to transformation of the cellular morphology. Furthermore, the cellular morphology did not obviously transform with an increase in the microemulsion concentration. Pharmaceutical adjuncts of the prepared microemulsion, such as PEG-400 (11.2%, w/w)39 and Cremophor EL (33.8%, w/w), are used extensively in the pharmaceutical industry. Cremophor EL use has been reported, up to the 50% level, as a solubilizer in preparations of paclitaxel injections,40 and when used in this study, no obvious transformation of cellular morphology was observed with an inverted microscope. Ethyl oleate is extensively used in topical medications and is designated by the US Food and Drug Administration as harmless, which is supported by the results of a 91-day feeding study in rats.41 This evidence supports the finding that the microemulsion has little cellular toxicity.

Bottom Line: Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions.Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle.The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai, The People's Republic of China.

ABSTRACT

Objective: To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures.

Materials and methods: A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity.

Results: The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed.

Conclusion: The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

Show MeSH
Related in: MedlinePlus