Citation: Iqbal Zoya, Haisheng He, Luting Wang, Jianping Qi, Yi Lu, Wei Wu. The intragastrointestinal fate of paclitaxel-loaded micelles: Implications on oral drug delivery[J]. Chinese Chemical Letters, ;2021, 32(4): 1545-1549. doi: 10.1016/j.cclet.2020.09.038 shu

The intragastrointestinal fate of paclitaxel-loaded micelles: Implications on oral drug delivery

Iqbal Zoya ^a ,
Haisheng He ^a ,
Luting Wang ^a ,
Jianping Qi ^a ,
Yi Lu ^a ,
Wei Wu ^{a, b, *,}

a.
Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China
b.
Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China

wuwei@shmu.edu.cn

Received Date: 5 August 2020
Revised Date: 21 September 2020
Accepted Date: 22 September 2020
Available Online: 23 September 2020

Figures(4)

The goal of the present study is to elucidate the intragastrointestinal fate of micellar delivery systems by monitoring fluorescently labeled different micelles and the model drug paclitaxel (PTX). Both in vitro and ex vivo leakage studies showed fast PTX release in fluids while micelles remained intact, except in fed-state simulated intestinal fluid and fasted-state pig intestinal fluid, thus referring to the intact absorption of micelles and PTX leakage in the gastrointestinal tract with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles showing higher stability than other micelles. All groups of micelles were absorbed intact in Caco-2 and Caco-2/HT29-MTX cell models and the absorption of TPGS micelles was found to be higher than other micelles. The transport of the micelles across Caco-2/Raji (1.6%–3.5%), Caco-2 (0.8%–1%), and Caco-2/HT29-MTX (0.58%–1%) cell monolayers further verified the absorption of micelles and their subsequent transport; however, more TPGS micelles transported across cell monolayers than other groups. Moreover, the histological examination also confirmed that micelles entered the enterocytes and were transported to basolateral tissues and TPGS showed the stronger ability of penetration than other groups. Thus, these results are succinctly presenting the absorption of intact micelles in GIT confirmed by imaging evidence with prior leakage of the drug, uptake by enterocytes and the transport of micelles that survive the digestion by enterocytes and mainly by microfold cells in material nature dependent way with TPGS showing better results than other groups. In conclusion, these results identify the mechanism by which the gastrointestinal tract processes micelles and point to the likely use of this approach in the design of micelles-based therapies.
- Drug delivery,
- Oral,
- Micelles,
- Paclitaxel,
- In vivo fate
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