Mayolo Deloisa, Karla PatriciaEscobar Fernández, Aleyda Margarita2025-06-242025Escobar Fernández, A. M. (2025) PEGylation of Silk Fibroin Nanoparticles for the Encapsulation of 3,3’-diindolylmethane in Route for the Treatment of Obesity [Tesis maestría] Instituto Tecnológico y de Estudios Superiores deMonterrey]. Repositorio Institucional del Tecnológico de Monterrey. Recuperado de: https://hdl.handle.net/11285/703770https://hdl.handle.net/11285/703770Obesity is responsible for 5 million deaths each year. Considering the complexity of the disease, alternative plant-based compounds, like 3,3´-diindolylmethane (DIM), have become of therapeutical interest. To overcome the poor bioavailability of DIM and enhance its delivery, silk fibroin nanoparticles (SFNP) can be employed. The aim of this work was to PEGylate DIM-loaded SFNP using 5 kDa p-nitrophenyl carbonate methoxy polyethylene glycol (mPEG-PNC), to reduce the previously reported cytotoxicity of SFNP. First, the optimal PEGylation conditions were determined by chromatographic, electrophoretic and computational methods. Silk fibroin (SF) showed higher flexibility, group availability and reactivity when using sodium borate buffer at pH 9.4, thus PEGylation was enhanced. These findings were applied on the PEGylation of SF and SFNP at different mass ratios with mPEG-PNC. After this analysis, PEGylation of DIM-loaded SFNP was performed under a mPEG:SFNP mass ratio of 6:1, achieving a PEGylation efficiency of 11.9 ± 7.79 %. These particles had a spherical shape with a size of 98.98 ± 1.97 nm, a surface charge of -30.86 ± 1.09 mV, and a polydispersity index of 0.18. The encapsulation efficiency of DIM in SFNP was 13.16 ± 4.74%, exceeding previous reports. Drug release analysis in physiological conditions suggests that PEGylation prolongued DIM liberation, even after 48 h. Finally, it was confirmed that PEGylated SFNP reduced cytotoxicity on 3T3-L1 preadipocytes, maintaining a 100% cell viability at all evaluated doses, unlike unmodified SFNP. These results demonstrate that PEGylated SFNP, under the developed methodology, can become a promising vehicle to enhance the delivery of DIM, for the treatment of obesity.TextoengopenAccesshttp://creativecommons.org/licenses/by-nc/4.0MEDICINA Y CIENCIAS DE LA SALUD::CIENCIAS MÉDICAS::OTRAS ESPECIALIDADES MÉDICAS::OTRASMedicineTesis de maestríaPublicación de artículo científicohttps://orcid.org/0009-0006-1080-9753Silk fibroin nanoparticlesPEGylation3,3'-diindolylmethaneObesityDrug deliveryCytotoxicity1317941