Preparation of Peppermint Oil-Based Nanodevices Loaded with Paclitaxel: Cytotoxic and Apoptosis Studies in HeLa Cells

• Published in: AAPS PharmSciTech Vol. 20; no. 5; p. 198
• Main Authors: Flores-Villaseñor, Sergio E., Peralta-Rodríguez, René D., Padilla-Vaca, Felipe, Meléndez-Ortiz, H. Iván, Ramirez-Contreras, Jorge C., Franco, Bernardo
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 24.05.2019
• Subjects: Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - pharmacokinetics; Apoptosis - drug effects; Apoptosis - physiology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Survival - drug effects; Cell Survival - physiology; Cytotoxins - chemical synthesis; Cytotoxins - pharmacokinetics; Dose-Response Relationship, Drug; Drug Liberation; HeLa Cells; Humans; Nanospheres - chemistry; Paclitaxel - chemical synthesis; Paclitaxel - pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Plant Oils - chemical synthesis; Plant Oils - pharmacokinetics; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - pharmacokinetics; Research Article; Surface-Active Agents - chemical synthesis; Surface-Active Agents - pharmacokinetics; Vitamin E - chemical synthesis; Vitamin E - pharmacokinetics; paclitaxel; microemulsions; nanodevices; drug delivery; cytotoxicity; peppermint oil
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-019-1399-7

In this work, several normal, oil-in-water (o/w) microemulsions (MEs) were prepared using peppermint essential oil, jojoba oil, trans -anethole, and vitamin E as oil phases to test their capacity to load paclitaxel (PTX). Initially, pseudo-ternary partial phase diagrams were constructed in order to find the normal microemulsion region using d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-1000) as surfactant and isobutanol (iso-BuOH) as co-surfactant. Selected ME formulations were loaded with PTX reaching concentrations of 0.6 mg mL −1 for the peppermint oil and trans -anethole MEs, while for the vitamin E and jojoba oil MEs, the maximum concentration was 0.3 mg mL −1 . The PTX-loaded MEs were stable according to the results of heating–cooling cycles and mechanical force (centrifugation) test. Particularly, drug release profile for the PTX-loaded peppermint oil ME (MEPP) showed that ∼ 90% of drug was released in the first 48 h. Also, MEPP formulation showed 70% and 90% viability reduction on human cervical cancer (HeLa) cells after 24 and 48 h of exposure, respectively. In addition, HeLa cell apoptosis was confirmed by measuring caspase activity and DNA fragmentation. Results showed that the MEPP sample presented a major pro-apoptotic capability by comparing with the unloaded PTX ME sample.