Publicação
Lactobionic Acid - Chitosan Nanoparticles As a Delivery System for Curcumin
| Resumo: | Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa, also known asTurmeric. It has good therapeutic properties such as anti- anti-carcinogenic, chemoprotectiveanti-inflammatory and antioxidant effects. However, despite its benefits, it has low aqueoussolubility, and consequently poor bioavailability. One strategy to overcome this encapsulating the curcumin into a drug delivery system, like micro- or nanoparticles.The nanoparticles (NPs) have increased their importance since they can improve the properties of certain therapeutic active molecules, like their retention time in the local ofadministration, allowing a more controllable drug release, or even providing a more specialized targeting. Among diverse polymers, carbohydrates, and chitosan in particular, have been intensively used. Chitosan results from the deacetylation of chitin and is a polymer consisting of alternating β (1-4) linked N-acetyl-D-glucosamine and D-glucosamine residues. It has many applications based on biological activities such as mucoadhesive and, immunostimulating properties. In the literature, chitosan NPs have been used in areas like, vaccines or cancer treatment, as a delivery system. This work aims to develop chitosan NPs loading curcumin to target the hepatocellular carcinoma. For that the chitosan was chemically associated with the lactobionic acid (LA) as a ligand to bind to the receptor asialoglycoprotein (ASGPR). The thesis described the production of chitosan NPs modified with lactobionic acid encapsulating curcumin. These NPs were then tested on cells and then compared with non-modified chitosan particles.The NPs had a low polydispersity index (PDI), 0.261 for ChiCas, 0.418 for ChiCas-Cur, 0.188for LA-modified ChiCas and 0.193 for LA-modified ChiCas-Cur, with a small size, 326.9 nmfor ChiCas, 499.2 nm for ChiCas-Cur, 207.3 nm for LA-modified ChiCas and 203.3 nm forLA-modified ChiCas-Cur. In terms of the zeta potential, all NPs presented a positive zetapotential with values 37.1 mV for ChiCas, 42.1 mV for ChiCas-Cur, 44.1 mV for LA-modified ChiCas and 40.9 mV for LA-modified ChiCas-Cur, presenting minor variations between batches. Based on the SEM analysis, the NPs also showed a round shape morphology. After the characterization of the NPs, the immunotoxicity and immunomodulatory effects were evaluated in two different cell types, THP-1 cells and HepG2 cells. THP-1 cells were used to study the effect of the NPs on our immune system, and the HepG2 cells were used to study the effect of the NPs with the presence of the LA on the cells of the liver (hepatocytes). The results of the studies showed that none of the NPs were toxic for the cells.Furthermore, the production of HepG2 spheroids, to test the same formulations, were implemented in the laboratory to confirm the results. The results obtained demonstrated that the NPS did not exhibit toxicity towards the spheroids. |
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| Autores principais: | Pedro, Inês Catarina do Ó |
| Assunto: | Curcumin Chitosan Delivery systems Nanoparticles Lactobionic acid. Curcumina Quitosano Sistemas de entrega Nanoparticulas Ácido Lactobiónico |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa, also known asTurmeric. It has good therapeutic properties such as anti- anti-carcinogenic, chemoprotectiveanti-inflammatory and antioxidant effects. However, despite its benefits, it has low aqueoussolubility, and consequently poor bioavailability. One strategy to overcome this encapsulating the curcumin into a drug delivery system, like micro- or nanoparticles.The nanoparticles (NPs) have increased their importance since they can improve the properties of certain therapeutic active molecules, like their retention time in the local ofadministration, allowing a more controllable drug release, or even providing a more specialized targeting. Among diverse polymers, carbohydrates, and chitosan in particular, have been intensively used. Chitosan results from the deacetylation of chitin and is a polymer consisting of alternating β (1-4) linked N-acetyl-D-glucosamine and D-glucosamine residues. It has many applications based on biological activities such as mucoadhesive and, immunostimulating properties. In the literature, chitosan NPs have been used in areas like, vaccines or cancer treatment, as a delivery system. This work aims to develop chitosan NPs loading curcumin to target the hepatocellular carcinoma. For that the chitosan was chemically associated with the lactobionic acid (LA) as a ligand to bind to the receptor asialoglycoprotein (ASGPR). The thesis described the production of chitosan NPs modified with lactobionic acid encapsulating curcumin. These NPs were then tested on cells and then compared with non-modified chitosan particles.The NPs had a low polydispersity index (PDI), 0.261 for ChiCas, 0.418 for ChiCas-Cur, 0.188for LA-modified ChiCas and 0.193 for LA-modified ChiCas-Cur, with a small size, 326.9 nmfor ChiCas, 499.2 nm for ChiCas-Cur, 207.3 nm for LA-modified ChiCas and 203.3 nm forLA-modified ChiCas-Cur. In terms of the zeta potential, all NPs presented a positive zetapotential with values 37.1 mV for ChiCas, 42.1 mV for ChiCas-Cur, 44.1 mV for LA-modified ChiCas and 40.9 mV for LA-modified ChiCas-Cur, presenting minor variations between batches. Based on the SEM analysis, the NPs also showed a round shape morphology. After the characterization of the NPs, the immunotoxicity and immunomodulatory effects were evaluated in two different cell types, THP-1 cells and HepG2 cells. THP-1 cells were used to study the effect of the NPs on our immune system, and the HepG2 cells were used to study the effect of the NPs with the presence of the LA on the cells of the liver (hepatocytes). The results of the studies showed that none of the NPs were toxic for the cells.Furthermore, the production of HepG2 spheroids, to test the same formulations, were implemented in the laboratory to confirm the results. The results obtained demonstrated that the NPS did not exhibit toxicity towards the spheroids. |
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