학술논문
Pegylated liposome encapsulating docetaxel using microfluidic mixing technique: Process optimization and results in breast cancer models.
Document Type
Academic Journal
Author
Dacos M; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France; Assitance Publique des Hôpitaux de Marseille, Marseille, France. Electronic address: Mathilde.dacos@ap-hm.fr.; Immordino B; Fondazione Pisana per La Scienza, 56017 San Giuliano, Pisa, Italy.; Diroff E; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France.; Sicard G; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France; Assitance Publique des Hôpitaux de Marseille, Marseille, France.; Kosta A; Microscopy Core Facility, Institut de Microbiologie de la Méditerranée (FR3479), CNRS, Aix-Marseille Université, Marseille, France.; Rodallec A; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France.; Giacometti S; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France.; Ciccolini J; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France; Assitance Publique des Hôpitaux de Marseille, Marseille, France.; Fanciullino R; COMPO, SMARTc. CRCM: UMR Inserm 1068, CNRS UMR 7258, AMU U105, IPC, Marseille, France; Assitance Publique des Hôpitaux de Marseille, Marseille, France.
Source
Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
Subject
Language
English
Abstract
The development of nanoparticles could help to improve the efficacy/toxicity balance of drugs. This project aimed to develop liposomes and immunoliposomes using microfluidic mixing technology.Various formulation tests were carried out to obtain liposomes that met the established specifications. The liposomes were then characterized in terms of size, polydispersity index (PDI), docetaxel encapsulation rate and lamellarity. Antiproliferative activity was tested in human breast cancer models ranging from near-negative (MDA-MB-231), positive (MDA-MB-453) to HER2 positive. Pharmacokinetic studies were performed in C57BL/6 mice.Numerous batches of liposomes were synthesised using identical molar ratios and by varying the microfluidic parameters TFR, FRR and buffer. All synthesized liposomes have a size < 200 nm, but only Lipo-1, Lipo-6, Lipo-7, Lipo-8 have a PDI < 0.2, which meets our initial requirements. The size of the liposomes was correlated with the total FRR, for a 1:1 FRR the size is 122.2 ± 12.3 nm, whereas for a 1:3 FRR the size obtained is 163.4 ± 34.0 nm (p = 0.019. Three batches of liposomes were obtained with high docetaxel encapsulation rates > 80 %. Furthermore, in vitro studies on breast cancer cell lines demonstrated the efficacy of liposomes obtained by microfluidic mixing technique. These liposomes also showed improved pharmacokinetics compared to free docetaxel, with a longer half-life and higher AUC (3-fold and 3.5-fold increase for the immunoliposome, respectively).This suggests that switching to the microfluidic process will produce batches of liposomes with the same characteristics in terms of in vitro properties and efficacy, as well as the ability to release the encapsulated drug over time in vivo. This time-efficiency of the microfluidic technique is critical, especially in the early stages of development.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mathilde Dacos reports administrative support was provided by Aix-Marseille University. Mathilde Dacos reports a relationship with Aix-Marseille University that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mathilde Dacos reports administrative support was provided by Aix-Marseille University. Mathilde Dacos reports a relationship with Aix-Marseille University that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)