New technology for the production of chemotherapeutic nanotransport

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New technology for the production of chemotherapeutic nanotransport

Wednesday, 04.09.2019

Cláudia Martins1,2,3 e Bruno Sarmento1,2,4

1 I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

2 INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal

3 ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

4 CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal

Taxane chemotherapeutics have played a key role in the treatment of various types of cancer throughout the past years. However, the drawbacks inherent to the pharmaceutical formulation of taxanes are still a reality and mainly due to the low aqueous solubility of these medicines, as well as to the nontargeted therapy and consequent side effects. Nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) have sparked broad interest in this field and demonstrated capacity of improving taxanes’ formulation. If, in one hand, the PLGA core of these NPs is able to solubilize drugs, on the other hand, the PEG shell promotes immune escape and presents chemical end groups for the attachment of targeting ligands. Advances in the design of these nanosystems resulted in the development of multitargeted PLGA/PEG NPs achieved by dual-ligand functionalization. The multitargeting offers a promising alternative to the delivery of taxanes across successive cell types or compartments and to the synergetic exploitation of more than one transporter on the cell surface. Besides the upgrade in the design of multitargeted PLGA/PEG NPs, their manufacturing has also evolved from bulk assembly to continuous-flow, high-throughput technologies such as microfluidics. This technology relies on microchannel platforms described to enable the production of large-scale batches of NPs in a better time-saving manner, with higher drug loading, reproducibility, and lower polydispersity. Herein, a detailed microfluidic method for the preparation of multitargeted, taxane-loaded PLGA/PEG NPs is described. Focus is given to the setting up of the microfluidic system and conditions required to manufacture these NPs by using polymers of PLGA and PEG previously elsewhere functionalized with two generic targeting ligands.

Methods in Molecular Biology