Publicação
Development of PEGylated nanoparticles for delivery of methotrexate derivatives
| Resumo: | Cancer is one of the most devastating and life-threatening diseases, and conventional chemotherapeutic agents, such as methotrexate (MTX), present several limitations and adverse effects. The use of nanoparticles (NPs) enables an efficient alternative to conventional therapy as they can overcome these limitations. NPs may be engineered to have a prolonged circulation time, enhanced cellular uptake and targeting abilities. One widely used targeting approach is the development of NPs containing folic acid (FA) at the surface. Folate receptor (FR) is overexpressed in tumor cells and is not expressed or is present at low levels in normal cells. In this way, FA-tagged NPs allow a specific delivery of the drug. Although several types of NPs have been developed as drug delivery systems (DDS), this work focused on the polymeric micelles and liposomes. Thus, the main aim of this project was the development of PEGylated micelles and liposomes with suitable characteristics for intravenous (IV) administration and with the ability to delivery hydrophobic MTX derivatives to a target cell population. First of all, micelles and liposomes production methods were optimized. For the micelles production were tested two different methods, auxiliary solvent method and sonication, and the liposomes were produced using ethanol injection method. The full characterization of the developed NPs was performed, including the analysis of their physicochemical properties, stability, drug encapsulation efficiency (EE) and biological effect. The use of the auxiliary solvent method with evaporation at 30 ºC, a polyoxyethanyl-α-tocopheryl sebacate (PTS) concentration of 15 mg/mL and a PTS/MTX diethylated (MTX-OEt) mass ratio of 8:1 resulted in monodisperse micelles with small size. These PEGylated micelles revealed the expected biological effect against cancer cells (Caco-2 cells). In the case of liposomes, the ideal formulation was reached using a lipid concentration of 9 mM, water as aqueous phase, a MTXdimethyldioctadecylammonium bromide (MTX-DODAB) concentration of 2.91 mg/mL and an initial water/ethanol volume of 6/6 mL. The obtained liposomes also showed suitable characteristics including a monodisperse population of small and neutral particles and demonstrated a significant cytotoxicity against cancer cells, similar to free MTX. In sum, the developed PEGylated micelles and liposomes loaded with hydrophobic MTX derivatives demonstrated to be promising DDS for cancer therapy. |
|---|---|
| Autores principais: | Cerqueira, Patrícia Alexandra Gomes |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866876175246163968 |
|---|---|
| author | Cerqueira, Patrícia Alexandra Gomes |
| author_facet | Cerqueira, Patrícia Alexandra Gomes |
| author_role | author |
| contributor_name_str_mv | Loureiro, Ana Isabel Sá Marcos, João Carlos Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Cerqueira, Patrícia Alexandra Gomes\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Loureiro, Ana Isabel Sá Marcos, João Carlos Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Cerqueira, Patrícia Alexandra Gomes |
| datacite.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-01-01T07:00:36Z |
| datacite.date.embargoed.fl_str_mv | 2022-01-01T07:00:36Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | Development of PEGylated nanoparticles for delivery of methotrexate derivatives Desenvolvimento de nanopartículas peguiladas para a entrega de derivados de metotrexato |
| dc.contributor.none.fl_str_mv | Loureiro, Ana Isabel Sá Marcos, João Carlos Universidade do Minho |
| dc.creator.none.fl_str_mv | Cerqueira, Patrícia Alexandra Gomes |
| dc.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-01-01T07:00:36Z |
| dc.date.embargoed.fl_str_mv | 2022-01-01T07:00:36Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/65119 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.title.fl_str_mv | Development of PEGylated nanoparticles for delivery of methotrexate derivatives Desenvolvimento de nanopartículas peguiladas para a entrega de derivados de metotrexato |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Cancer is one of the most devastating and life-threatening diseases, and conventional chemotherapeutic agents, such as methotrexate (MTX), present several limitations and adverse effects. The use of nanoparticles (NPs) enables an efficient alternative to conventional therapy as they can overcome these limitations. NPs may be engineered to have a prolonged circulation time, enhanced cellular uptake and targeting abilities. One widely used targeting approach is the development of NPs containing folic acid (FA) at the surface. Folate receptor (FR) is overexpressed in tumor cells and is not expressed or is present at low levels in normal cells. In this way, FA-tagged NPs allow a specific delivery of the drug. Although several types of NPs have been developed as drug delivery systems (DDS), this work focused on the polymeric micelles and liposomes. Thus, the main aim of this project was the development of PEGylated micelles and liposomes with suitable characteristics for intravenous (IV) administration and with the ability to delivery hydrophobic MTX derivatives to a target cell population. First of all, micelles and liposomes production methods were optimized. For the micelles production were tested two different methods, auxiliary solvent method and sonication, and the liposomes were produced using ethanol injection method. The full characterization of the developed NPs was performed, including the analysis of their physicochemical properties, stability, drug encapsulation efficiency (EE) and biological effect. The use of the auxiliary solvent method with evaporation at 30 ºC, a polyoxyethanyl-α-tocopheryl sebacate (PTS) concentration of 15 mg/mL and a PTS/MTX diethylated (MTX-OEt) mass ratio of 8:1 resulted in monodisperse micelles with small size. These PEGylated micelles revealed the expected biological effect against cancer cells (Caco-2 cells). In the case of liposomes, the ideal formulation was reached using a lipid concentration of 9 mM, water as aqueous phase, a MTXdimethyldioctadecylammonium bromide (MTX-DODAB) concentration of 2.91 mg/mL and an initial water/ethanol volume of 6/6 mL. The obtained liposomes also showed suitable characteristics including a monodisperse population of small and neutral particles and demonstrated a significant cytotoxicity against cancer cells, similar to free MTX. In sum, the developed PEGylated micelles and liposomes loaded with hydrophobic MTX derivatives demonstrated to be promising DDS for cancer therapy. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/71c084a2-1888-4c56-a70f-8a759f0f7e98/download |
| id | rum_1f712673acbca0c75ea985d971bcaa1e |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/65119 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
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| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/65119 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Cerqueira, Patrícia Alexandra Gomes |
| publishDate | 2018 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporCancer is one of the most devastating and life-threatening diseases, and conventional chemotherapeutic agents, such as methotrexate (MTX), present several limitations and adverse effects. The use of nanoparticles (NPs) enables an efficient alternative to conventional therapy as they can overcome these limitations. NPs may be engineered to have a prolonged circulation time, enhanced cellular uptake and targeting abilities. One widely used targeting approach is the development of NPs containing folic acid (FA) at the surface. Folate receptor (FR) is overexpressed in tumor cells and is not expressed or is present at low levels in normal cells. In this way, FA-tagged NPs allow a specific delivery of the drug. Although several types of NPs have been developed as drug delivery systems (DDS), this work focused on the polymeric micelles and liposomes. Thus, the main aim of this project was the development of PEGylated micelles and liposomes with suitable characteristics for intravenous (IV) administration and with the ability to delivery hydrophobic MTX derivatives to a target cell population. First of all, micelles and liposomes production methods were optimized. For the micelles production were tested two different methods, auxiliary solvent method and sonication, and the liposomes were produced using ethanol injection method. The full characterization of the developed NPs was performed, including the analysis of their physicochemical properties, stability, drug encapsulation efficiency (EE) and biological effect. The use of the auxiliary solvent method with evaporation at 30 ºC, a polyoxyethanyl-α-tocopheryl sebacate (PTS) concentration of 15 mg/mL and a PTS/MTX diethylated (MTX-OEt) mass ratio of 8:1 resulted in monodisperse micelles with small size. These PEGylated micelles revealed the expected biological effect against cancer cells (Caco-2 cells). In the case of liposomes, the ideal formulation was reached using a lipid concentration of 9 mM, water as aqueous phase, a MTXdimethyldioctadecylammonium bromide (MTX-DODAB) concentration of 2.91 mg/mL and an initial water/ethanol volume of 6/6 mL. The obtained liposomes also showed suitable characteristics including a monodisperse population of small and neutral particles and demonstrated a significant cytotoxicity against cancer cells, similar to free MTX. In sum, the developed PEGylated micelles and liposomes loaded with hydrophobic MTX derivatives demonstrated to be promising DDS for cancer therapy.application/pdfengDevelopment of PEGylated nanoparticles for delivery of methotrexate derivativesAlternativeTitleporDesenvolvimento de nanopartículas peguiladas para a entrega de derivados de metotrexatoCerqueira, Patrícia Alexandra GomesLoureiro, Ana Isabel SáMarcos, João CarlosHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:2022786892022-01-01T07:00:36Z201820182018-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/65119http://purl.org/coar/access_right/c_abf2open access3319969 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/71c084a2-1888-4c56-a70f-8a759f0f7e98/download |
| spellingShingle | Development of PEGylated nanoparticles for delivery of methotrexate derivatives Cerqueira, Patrícia Alexandra Gomes |
| status | SINGLETON |
| title | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| title_full | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| title_fullStr | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| title_full_unstemmed | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| title_short | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| title_sort | Development of PEGylated nanoparticles for delivery of methotrexate derivatives |
| url | https://hdl.handle.net/1822/65119 |
| visible | 1 |