Preparation of parenteral nanocrystal suspensions of etoposide from the excipient free dry state of the drug to enhance in vivo antitumoral properties

Abstract

Nanoparticle technology in cancer chemotherapy is a promising approach to enhance active ingredient pharmacology and pharmacodynamics. Indeed, drug nanoparticles display various assets such as extended blood lifespan, high drug loading and reduced cytotoxicity leading to better drug compliance. In this context, organic nanocrystal suspensions for pharmaceutical use have been developed in the past ten years. Nanocrystals offer new possibilities by combining the nanoformulation features with the properties of solid dispersed therapeutic ingredients including (i) high loading of the active ingredient, (ii) its bioavailability improvement, and (iii) reduced drug systemic cytotoxicity. However, surprisingly, no antitumoral drug has been marketed as a nanocrystal suspension until now. Etoposide, which is largely used as an anti-cancerous agent against testicular, ovarian, small cell lung, colon and breast cancer in its liquid dosage form, has been selected to develop injectable nanocrystal suspensions designed to be transferred to the clinic. The aim of the present work is to provide optimized formulations for nanostructured etoposide solutions and validate by means of in vitro and in vivo evaluations the efficiency of this multiphase system. Indeed, the etoposide formulated as a nanosuspension by a bottom-up approach showed higher blood life span, reduced tumor growth and higher tolerance in a murine carcinoma cancer model. The results obtained are promising for future clinical evaluation of these etoposide nanosuspensions.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound—An In Vitro Study

“…Furthermore, after parenteral administration, the NPs can easily reach the tumor tissues because of the defective and leaky structure of tumor vessels, as well as the impaired lymphatic system. This phenomenon is known as enhanced permeability and retention effect (EPR) and allows the NPs to accumulate at the tumor site [14][15][16]. These characteristics make the NPs a promising approach to improve the efficacy of therapeutic cancer treatments [17].…”

Nano- and Crystal Engineering Approaches in the Development of Therapeutic Agents for Neoplastic Diseases

“…Etoposide (ETO) is an enzyme topoisomerase inhibitor that is largely utilized as a chemotherapeutic inhibitor for the treatment of ovarian cancer, lung cancer, breast cancer, testicular cancer, neuroblastoma, small lung cancer, and colon cancer [81]. It has very low water solubility and is often formulated together with a large proportion of cosolvents that lead to adverse effects [81]. Antisolvent precipitation method was utilized in preparing etoposide nanocrystal suspension [81].…”

“…It has very low water solubility and is often formulated together with a large proportion of cosolvents that lead to adverse effects [81]. Antisolvent precipitation method was utilized in preparing etoposide nanocrystal suspension [81]. The nanocrystals of ETO suspension demonstrated a sustained release drug profile kinetics in comparison to its marketed form [81].…”

Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy

“…Nanoparticle-based drug delivery systems provide various benefits, including longer half-life drug circulation, increased drug bioavailability, elevated solubility and better stability, controlled drug release and efficient targeting. [5][6][7][8] Therefore, nanoparticle-based drug delivery systems represent a promising vehicle for transporting anticancer drugs to cancer cells.…”