Polymeric micelles using cholinium-based ionic liquids for the encapsulation and release of hydrophobic drug molecules

Author(s)

Kurnik, Isabelle S. ^[1] ; D'Angelo, Natalia A. ^[2] ; Mazzola, Priscila G. ^[2] ; Chorilli, Marlus ^[3] ; Kamei, Daniel T. ^[4] ; Pereira, Jorge F. B. ^[5] ; Vicente, Antonio A. ^[6] ; Lopes, Andre M. ^[2]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Engn Bioproc & Biotechnol, Araraquara, SP - Brazil

^[2] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, Araraquara, SP - Brazil

^[4] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA - USA

^[5] Univ Coimbra, Dept Chem Engn, CIEPQPF, Coimbra - Portugal

^[6] Univ Minho, Ctr Biol Engn CEB, Braga - Portugal

• Document type: Journal article
• Source: BIOMATERIALS SCIENCE; v. 9, n. 6, p. 2183-2196, MAR 21 2021.
• Web of Science Citations: 0

Abstract

We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic (R) L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The partitioning of the hydrophobic model compound curcumin (CCM) into the PM-rich phase and the drug delivery capabilities of the PMs were investigated. ATPMSs formed using more hydrophobic ILs (i.e., {[}Ch]{[}Hex] approximate to {[}Ch]{[}But] > {[}Ch]{[}Pro] > {[}Ch]{[}Ac] approximate to {[}Ch]Cl) were the most effective in partitioning (K-CCM) and recovering (RECRich) CCM into the PM-rich phase (15.2 < K-CCM < 22.0 and 90% < RECRich < 95%, respectively). Moreover, using 1.2 M {[}Ch]{[}But] and 0.2 M {[}Ch]{[}Hex] ILs yielded higher encapsulation efficiency (EE) (94.1 and 96.0%, respectively) and drug loading (DL) capacity (14.8 and 16.2%, respectively), together with an increase in the average hydrodynamic diameter of the PMs (D-H) (42.5 and 45.6 nm, respectively). The CCM-PM formulations were stable at 4.0, 25.0, and 37.0 degrees C and the release of CCM was faster with the less hydrophobic ILs (i.e., {[}Ch]Cl and {[}Ch]{[}Ac]). Furthermore, due to the lower critical solution temperature properties of Pluronic (R) L35, the PMs exhibit temperature responsiveness at 37.0 degrees C. In vitro cytotoxicity assays were also performed to determine the potency of CCM-PM formulations, and a 1.8-fold decrease in IC50 values was observed between the CCM-PMs/{[}Ch]{[}Hex] and CCM-PMs/{[}Ch]Cl formulations for PC3 cells. The lower IC50 value for the {[}Ch]{[}Hex] version corresponded to a greater potency compared to the {[}Ch]Cl version, since a lower concentration of CCM was required to achieve the same therapeutic effect. The ATPMSs investigated in this study serve as a novel platform for Pluronic (R) L35/PBS buffer (pH 7.4) + IL-based ATPMS development. The unique properties reported here may be useful in applications such as controlled-release drug delivery systems (DDS), encapsulation, and bioseparations. (AU)

• FAPESP's process: 18/10799-0 - Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells
• Grantee: André Moreni Lopes
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 20/03727-2 - Polymersomes development aiming at the co-encapsulation of drugs for application in cancer therapy
• Grantee: Natalia Aimee D'Angelo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/16424-7 - Optimization and scale-up of liquid-liquid extraction process with ionic liquids (ILs) as a sustainable tool for the separation of the anti-leukemia biopharmaceutical L-asparaginase (ASPase)
• Grantee: Jorge Pereira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/05111-9 - Aqueous two-phase micellar systems based on ionic liquids as platforms for the curcumin encapsulation in polymeric micelles
• Grantee: Isabelle Souza Kurnik
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/05624-9 - Encapsulation and in vitro release studies of curcumin in polymeric micelles composed of PEO-PPO-PEO triblock copolymers
• Grantee: Isabelle Souza Kurnik
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• FAPESP's process: 17/10789-1 - Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells
• Grantee: André Moreni Lopes
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/08549-8 - Polymersomes decorated with transferrin and evaluation of their stability and drug release behavior
• Grantee: Mayra Caroline Cunha Câmara
• Support Opportunities: Scholarships in Brazil - Scientific Initiation