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. 2024 Dec 7;10(12):806.
doi: 10.3390/gels10120806.

Microgels of N-Isopropylacrylamide Copolymerized with an Amphiphilic Acid for the Delivery of Doxorubicin

Teresa G Rodriguez-Tellez  1 , Héctor Magaña  1 , José M Cornejo-Bravo  1 , Giovanni Palomino-Vizcaino  2 , Kenia Palomino-Vizcaino  1
Affiliations

Microgels of N-Isopropylacrylamide Copolymerized with an Amphiphilic Acid for the Delivery of Doxorubicin

Teresa G Rodriguez-Tellez et al. Gels. .

Abstract

This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox.

Keywords: doxorubicin; microgels; poly N-isopropylacrylamide; stimuli responsive materials.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
FTIR spectra of (A) CAM5 monomer, (B) MP, and (C) comparative spectra of the monomers used for the synthesis of MP.
Figure 1
Figure 1
FTIR spectra of (A) CAM5 monomer, (B) MP, and (C) comparative spectra of the monomers used for the synthesis of MP.
Figure 2
Figure 2
FESEM micrograph of MP 10% CAM5.
Figure 3
Figure 3
Temperature trends of (A) MP 5% CAM5, (B) MP 10% CAM5 and (C) MP 15% CAM5 in water, pH 3, pH 5, pH 7, and pH 9.
Figure 3
Figure 3
Temperature trends of (A) MP 5% CAM5, (B) MP 10% CAM5 and (C) MP 15% CAM5 in water, pH 3, pH 5, pH 7, and pH 9.
Figure 4
Figure 4
(A) Cumulative release of Dox at different conditions, (B) Dox-MP 10% CAM5.
Figure 5
Figure 5
In vitro cytotoxicity in HeLa cell line of (A) MP 10% CAM5 (without Dox), (B) Dox vs. Dox-MP 10% CAM5 and, (C) Dox-MP 10% CAM5 (37 vs. 42 °C). Data are presented as means ± SD (n = 5). * p 0.0366, **** p < 0.0001 vs. Dox. No statistically differences were detected among treating cells at different temperatures (ns).
Figure 6
Figure 6
Scheme of amphiphilic monomer CAM5 synthesis.
Figure 7
Figure 7
Schematic representation of the route synthesis of the microgels MP.
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