TY - JOUR
T1 - Biocompatible Ionic Liquid-Mediated Micelles for Enhanced Transdermal Delivery of Paclitaxel
AU - Ali, Md Korban
AU - Moshikur, Rahman Md
AU - Wakabayashi, Rie
AU - Moniruzzaman, Muhammad
AU - Goto, Masahiro
N1 - Funding Information:
The authors acknowledge the financial support (JSPS KAKENHI grant numbers JP16H06369 and JP20K20440) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The authors also thank the Government of Japan (MEXT, Japan) for providing a scholarship. We thank Frank Kitching, MSc., from the Edanz Group ( https://en-author-services.edanz.com/ac ) for editing a draft of this manuscript.
Publisher Copyright:
©
PY - 2021/5/5
Y1 - 2021/5/5
N2 - Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-πand π-πinteractions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.
AB - Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-πand π-πinteractions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.
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U2 - 10.1021/acsami.1c03111
DO - 10.1021/acsami.1c03111
M3 - Article
C2 - 33891816
AN - SCOPUS:85105906191
SN - 1944-8244
VL - 13
SP - 19745
EP - 19755
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 17
ER -
