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Microfluidic devices for drug nanocarriers formulation and evaluation

Gaia Pacassoni

Microfluidic devices for drug nanocarriers formulation and evaluation.

Rel. Gianni Ciofani, Lorenzo Albertazzi. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2018


Drug nanocarriers have gained a considerable attention in the development of cancer disease treatment. The nanoscale size and the capability of poorly water-soluble drug encapsulation, make nanoparticles a promising material for anti-cancer therapy. Drug encapsulation provides several advantages: the protection of the molecule against biological conditions and the possibility to deliver the therapeutic agent in the target region, limiting the side effects and enhancing the specificity and the efficiency of the treatment. Particle size, surface characteristics and drug release profile are fundamental aspects when designing an effective nanocarrier, as they define the drug delivery system performance. Therefore, the importance to control these features represents an issue of primary concern. Microfluidic devices are becoming a powerful tool in preparing drug nanocarriers, thanks to their capacity to formulate nanomaterials with controlled size distribution, low polydispersity index, and high batch-to-batch reproducibility. Poly lactic-co-glycolic acid (PLGA) is one of the most successfully developed biodegradable and biocompatible polymers, and shows great potential as principal component of polymeric drug delivery systems for parenteral route of administration. In addition, it can be conjugated with polyethylene glycol (PEG), giving rise to a block copolymer able to self-assemble into nanoscaled spheres. PEG corona, arranged on their surface, provides stealthness and allows eluding the immune system. According to the classical nucleation theory, nanoprecipitation is regulated by the mixing of solvent and antisolvent phases, and the particle size depends on the mixing times. Thus, microfluidic devices allow the control of this crucial parameter through the manipulation of the two phases flow rates. We focus on the use of microfluidic device-assisted nanoprecipitation method in a stabilizer-free process, which further simplifies post-processing steps and prevents side cytotoxic effects often caused by the presence of surfactant residuals. In the present work, we formulate PEG-PLGA nanoparticles using two different microfluidic devices and via bulk nanoprecipitation, as reference. While we observe the impossibility to tune the nanoparticle size through the manual process, we demonstrate that, optimizing the formulation parameters, the microfluidic approach allows obtaining a library of nanoparticles, owing a size range from 40 nm to 120 nm. Size distribution and polydispersity of the fabricated nanoparticles are characterized by means of dynamic light scattering and transmission electron microscopy. Moreover, model (drug/dye) molecules are encapsulated into the nanoparticles, and the encapsulation efficiency is quantitatively assessed by spectrophotometry. We demonstrate that the efficiency of encapsulation does not depend either on the nanoprecipitation technique or on the particle size, but only on the hydrophobicity of the molecule. Eventually, we conduct biological evaluations in order to ascertain that PEG-PLGA nanocarriers do not induce haemolysis, as they are meant to be injected into the blood stream. Further in vitro studies are carried out on MCF-7 adenocarcinoma breast cells for both plain and drug carrying particles; preliminary studies prove that the nanocarriers do not induce cell toxicity, however encapsulated doxorubicin decreases cells viability, confirming the suitability of the nanoparticles for anticancer applications.

Relators: Gianni Ciofani, Lorenzo Albertazzi
Academic year: 2018/19
Publication type: Electronic
Number of Pages: 88
Additional Information: Tesi secretata. Fulltext non presente
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Ente in cotutela: IBEC Barcellona (SPAGNA)
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/9762
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