Stereocomplexed PLA microspheres: Control over morphology, drug encapsulation and anticancer activity

Lung cancer is the leading cause of cancer death because of smoking and air pollution. Therefore, new ideas should be provided for lung cancer treatment in which the delivery of anticancer drugs to the local tumor site can be achieved. For this purpose, we propose the use of stereocomplexed spherica...

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Detalhes bibliográficos
Autores: Brzeziński, M., Kost, B., Wedepohl, S., Socka, M., Biela, T., Calderón, Marcelo
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/41960
Acesso em linha:http://hdl.handle.net/10810/41960
Access Level:acceso abierto
Palavra-chave:stereocomplex microspheres
morphology and size control
drug delivery systems
anticancer activity
proline
polylactides
polymerization
cancer
crystallization
nanoparticles
doxorubicin
stability
acid
Descrição
Resumo:Lung cancer is the leading cause of cancer death because of smoking and air pollution. Therefore, new ideas should be provided for lung cancer treatment in which the delivery of anticancer drugs to the local tumor site can be achieved. For this purpose, we propose the use of stereocomplexed spherical microspheres with sizes between 0.5 and 10 mu m loaded with doxorubicin (DOX) to be administered through the nasal route. In order to gain control over the microsphere morphology, size, and drug loading capacity, we systematically studied the influence of the solvent used for preparation and the functionalization of their building blocks, namely poly-L-lactide (PLLA) and poly-D-lactide (PDLA) with blocked or unblocked L-proline moieties. We could demonstrate that DOX release is generally determined by the size of the microspheres. The antiproliferative activity of DOX released from the different microspheres was shown in vitro using the A549 lung cancer cell line as a model. Moreover, when in direct contact to the cancer cells, smaller microspheres were uptaken and could serve as a reservoir for local drug release. Our findings not only provide a novel strategy to prepare PLA microspheres with controllable morphology and release of anti-cancer drugs but also offer additional possibilities for the application of stereocomplexed particles in anticancer therapy, with suitable sizes for nasal administration.