Microemulsions for Intravesical Delivery of Gemcitabine

Abstract

The objective of this work was to develop a safe and effective delivery vehicle for topical treatment of gemcitabine. The physicochemical properties, drug release rate, drug level in plasma and bladder, and histological changes of tissue after drug administration were investigated. The electrical conductivity, mean size, and viscosity of drug-loaded microemulsions were 0.8-102.0 mS/cm, 116.8-322.5 nm, and 42.9-105.0 cps؋10 3 , respectively. Gemcitabine loaded microemulsions showed a slower and sustained release. After intravesical administration of aqueous control and microemulsions treated, the drug concentrations in plasma were 15.11 mg/ml and 2.81-12.82 mg/ml, respectively, and the accumulation in bladder were 18.27 mg and 9.12-64.16 mg, respectively. Microemulsions slightly decreased the systemic absorption and significantly enhanced the accumulation in bladder tissue. Moreover, the preliminary toxicity studies revealed no overt adverse histological changes or tissue irritation by the microemulsion application. Therefore, the microemulsions were suggested to be a promising drug carrier for intravesical chemotherapy.

The Apoptotic Effect of Gemcitabine-Loaded-Microemulsion (Isopropyl Myristate/Tween 80/Span 20/Water/Ethanol) on A549 Non-Small Cell Lung Cancer Cells

“…The best formula was the hydrophobic delivery, MEb10+, which increased the mortality of the cells when compared with all of the drug formulas. Tsai et al (2010) produced three GEM-loaded-ME formulas that release GEM at different rates depending on the fraction of the ME components. The release rates of MEa, MEb, and MEc were 630.1 55.0, 390.3 96.2, and 141.1 9.6 mg cm 2 h 1/2 , respectively.…”

“…Furthermore, it is worth noting that a phase II study of intravesical GEM dissolved in alkaline solution demonstrated that GEM underwent crystallization under certain conditions, high pH, addition of sodium bicarbonate and storage at low temperature, which minimized the amount of GEM subjected into the syringes (Manners et al 2011). The objective of the present study was to evaluate the ME formulations, designed by Tsai et al (2010), in vitro. The ME formulas consisted of isopropyl myristate (IPM) as the oil phase, a surfactant mixture of polyoxyethylene sorbitan monooleate (tween 80) and sorbitan monolaurate (span 20), and an aqueous phase of distilled water and cosurfactant of ethanol.…”

“…A recent form of drug delivery for GEM was proposed by Tsai et al (2010) which was ME formulations that differ in composition. MEs are defined as a mixture of water, oil, and an amphiphile which is optically isotropic and thermodynamically stable and does not require energy for the dispersion process.…”

“…Additionally, MEs do not cause emboli formation in the blood and are less painful on injections relative to other co-solvent formulations. In fact, Tsai et al (2010) used a catheter to administer GEM-loaded-MEs for treating bladder cancer, which is the regular method used in treating such cancer.…”

Anticancer activities of tanshinone microemulsion against hepatocellular carcinoma in vitro and in vivo

“…Phospholipid, ethyl oleate, glycerol and pluronic F68 are biocompatible components of the Tan ME that can be safely used for i.v. injection (16,17). The surfactant enhances the permeability of the ME.…”