P(MMA‐co‐AA) Nanoparticles Loaded with Clioquinol and Functionalized with TAT Peptide

Abstract

Polymer nanoparticles produced through miniemulsion polymerizations can be used for design of drug encapsulation and targeted delivery systems. Particularly, the immobilization of functional groups on the surfaces of polymeric nanoparticles enables the development of targeted delivery systems, intended for particle absorption by specific body tissues, favoring the treatment of diseases. For this reason, in the present work poly(methyl methacrylate-co-acrylic acid) (P(MMA-co-AA)) nanoparticles loaded with clioquinol are prepared through in situ miniemulsion polymerizations for the first time. Besides, nanoparticles are functionalized with a cell-penetrating trans-activating transcriptor (TAT) peptide for the first time, to show that incorporation of carboxylic groups (from acrylic acid (AA)) on the particle surfaces provides an effective route for functionalization of nanoparticles with biomolecules. Particularly, it is shown that spherical particles with average sizes between 60 and 100 nm and zeta potential of −50 mV are produced and that the TAT peptide is successfully immobilized onto the particle surfaces. Besides, it is also shown that the clioquinol encapsulation efficiency is equal to 97%. In vitro tests show that 50% of the initial load of clioquinol is released after 9 h of test.

Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

“…Finally, DDSs have also been proposed for CQ or other HQ derivatives but we are far from achieving analogous results to those obtained for DSF (Wang et al, 2013;Weerasuriya et al, 2017;Wehbe et al, 2018;Campos et al, 2020). Nevertheless, the development of a selective DDS for CQ could be a turning point to solve the toxicity problems that led to the CQ withdrawal from the market.…”

In situ encapsulation of biologically active ingredients into polymer particles by polymerization in dispersed media

“…Furthermore, a pharmacokinetic study on rats showed improved bioavailability of the drug encapsulated in the NPs compared to a suspension of HPCT, which is promising for the use these NPs as oral drug delivery nanocarriers. Styrene (S) and MMA-based matrices are commonly used for the entrapment of hydrophobic active ingredients [87][88][89][90][91][92] via direct miniemulsion polymerization at high solids content (around 10-20 wt %), using AIBN or KPS as initiator. As discussed previously, a comonomer can be introduced to adjust the hydrophilicity of the polymer matrix and improve the EE.…”

“…For instance, in case of clioquinol encapsulation, cell-penetrating trans-activating transcriptor (TAT) was successfully immobilized via the carboxylic groups of P(AA-co-S) NSs to enhance the passage of nanoparticles through the blood brain barrier. [88] In other hand, a hydrophilic enzyme (CaIB) can be used in direct miniemulsion polymerization. The enzyme was first dissolved in the aqueous continuous phase and further immobilized on the surface of PMMA NSs after polymerization (Figure 17).…”

Development of a Clioquinol Nanocarrier as a New, Promising Option for the Treatment of Dermatomycosis

“…In this context, the use of nanotechnology in topical formulations can bring more advantages since it allows a topical therapy of the infection site with minimal drug absorption or systemic side effects [ 29 , 32 , 33 ]. Since CQ is highly lipophilic and it is not soluble in water, its incorporation in nanostructured systems is interesting and has been described previously [ 12 , 34 , 35 , 36 , 37 ]. However, these studies did not evaluate the use of CQ as an antifungal agent but focused on its use as an option for the treatment of neurodegenerative diseases [ 12 , 34 , 35 , 36 , 37 ].…”

“…Since CQ is highly lipophilic and it is not soluble in water, its incorporation in nanostructured systems is interesting and has been described previously [ 12 , 34 , 35 , 36 , 37 ]. However, these studies did not evaluate the use of CQ as an antifungal agent but focused on its use as an option for the treatment of neurodegenerative diseases [ 12 , 34 , 35 , 36 , 37 ]. Moreover, no study exploring lipid-based nanocarriers to load CQ were published to date.…”