New drug-delivery system shows promise for lung cancer

Researchers verified the drug-delivery benefits of the new PTX-HS15/T80 mixed-micelle system (PTX-HS15/T80 MMs), which improved the solubilization potential of paclitaxel (Taxol) injection. The group formulated the new system by combining HS15 and T80, and published the current results of the preclinical study in AAPS PharmSciTech.

The investigators based the development and testing of this novel mixed-micelle system on the theory of synergistic solubilization.

“Based on the theory of synergistic solubilization, the mixed micelle system composed of two or more materials reveals better properties than the traditional micelle, which consist[s] of single carrier material,” the authors wrote. 

According to the authors, mixed micelles offer the advantages of small size, strong solubilization ability, safety and economy, simple preparation, dense structure, enhanced solubilization effect, and high utilization rate of carrier materials. They wrote that the mixture of two prime surfactants facilitates the development of a formidable delivery system of insoluble drugs.

Researchers have previously demonstrated that using mixed micelles can significantly enhance the solubility, bioavailability, and therapeutic effect of hydrophobic drugs.

In the current study, the team investigated the potential advantages of the mixed-micelle delivery system using in vitro cytotoxicity testing and animal testing to elucidate the antineoplastic effects and in vivo actions of the system. Of note, in vitro cytotoxicity tests were performed using HeLa cell lines. Pharmacokinetic tests were done using rats, and tissue distribution studies were performed in mouse models.

Researchers showed that PTX-HS15/T80 MMs outperformed paclitaxel (Taxol) injection, which is a single-micelle preparation of paclitaxel, in terms of anticancer cell proliferation and lung tissue distribution. Furthermore, the novel delivery system demonstrated good blood clearance, low cardiotoxicity, and no sensitization, thus supporting the superiority of PTX-HS15/T80 MMs with regard to safety and efficacy. Importantly, the complex of surfactants present in this novel agent could serve as an effective strategy to develop new delivery systems in the future, according to the authors.

Compared with single-micelle paclitaxel, PTX-HS15/T80 MMs distributed well in the lung but to a low extent in the heart, as demonstrated by in vivo tissue distribution testing. Taken together, these results indicated that the novel mixed-micelle delivery system may be useful in treating lung cancer with a decreased risk of toxic side effects. Furthermore, the mixed-micelle model is simple and cheap to develop, and in vitro and in vivo advantages make for a good choice in resolving the issue of insoluble drug delivery.

Paclitaxel is a natural antitumor drug with unique mechanisms and efficacy. It is used in the prevention and treatment of non-small cell lung cancer, breast cancer, and ovarian cancer. Despite its utility, this drug has poor water solubility, which makes it hard to deliver in vivo. To date, researchers have tried to solubilize the drug via cosolvent systems, prodrug development, nanoparticles, nanosystems, microemulsion, or macromolecular complexes.

Paclitaxel injection is a single-micelle preparation that requires pretreatment with corticosteroids or antihistamines due to the carrier Cremophor EL (CrEL) being employed in its preparation. CrEL can activate human serum complement, release histamine, and trigger asymptomatic arrhythmia. Furthermore, the carrier can dissolve the plasticizer located in the PVC infusion bag, thus leading to severe hepatotoxicity. 

These issues motivated researchers to develop a paclitaxel formulation without CrEL. These included Abraxane, an albumin-binding paclitaxel nanoparticle preparation; Lipusu, a liposome composed of phosphatidylcholine and phosphatidylglycerol; and the polymeric micelle Genexol-PM. 

Although these new formulations are safer than paclitaxel, along with being somewhat more effective, they require complex and expensive preparation and quality control. In contrast, PTX-HS15/T80 MMs was developed as a low-toxicity, high-efficiency, and cheaper paclitaxel alternative.