Abstract
Limited drug penetration into solid tumors has been one of the potential causes of resistance to chemotherapy for the treatment of bladder cancer. The aim of the studies was to develop non-toxic nanoemulsion carriers of paclitaxel and to evaluate their ability to serve as a tool increasing and/or controlling the penetration of paclitaxel through the bladder tissue.
Various oil-in-water non-toxic self-nanoemulsifying formulations (SNEFs) were developed using Cremercoor MCT, Kollisolv MCT, Miglyol 812, 810, Capmul MCM, Imwitor 988, Imwitor 742 with TO106V, Tween 85, HCO30, Kolliphor EL and Cremophor RH40 at size ranges from approximately 19 to 110 nm that are capable of enhancing the solubility and stability of paclitaxel. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEFs. Paclitaxel was added with the oil/surfactant mixture before dispersing the mixture in water to form SNEF. The penetration study of the optimal SNEFs formulation was compared with the raw paclitaxel dispersion using transwell apparatus.
Initial characterisation and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 with water-soluble surfactant (high HLB) containing formulations generated highly efficient SNEFs as they are stable and produced lower nanodroplets with higher drug loading. The results have demonstrated that the SNEFs have good ability to retain its characteristics under conditions similar to that found in the urinary bladder up to 48 h. However, the results also showed that chemosensitivity of cancer cells exposed to paclitaxel was attenuated in the presence of SNEFs. Larger size SNEFs have shown to induce more inhibitory effects on paclitaxel activity. The reduction effects of SNEFs on doxorubicin (a relatively water-soluble drug) efficacy were almost absent, indication a poor loading of such compounds.
The reduction of the efficacy of SNEF loaded treatments does not give a strong indication of their ability to penetrate as examined their ability to penetrate through the cultivated multicell layers (MCL) of bladder cancer. However, these results may open the horizon to reflect the use of SNEFs in the introduction of intravenous paclitaxel because of its potential role in reducing the injection site toxicity.
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