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Tesi etd-11222023-104440


Tipo di tesi
Tesi di laurea magistrale
Autore
SCAIELLA, ESTER
URN
etd-11222023-104440
Titolo
Synthesis and self-assembling properties of amphiphilic random copolymers and their potential application as nanocarriers of an highly hydrophobic drug
Dipartimento
CHIMICA E CHIMICA INDUSTRIALE
Corso di studi
CHIMICA INDUSTRIALE
Relatori
relatore Prof.ssa Martinelli, Elisa
Parole chiave
  • Amphiphilic copolymers
  • Combretastatin A-4
  • drug delivery
  • nanocarriers
  • unimer micelles
Data inizio appello
11/12/2023
Consultabilità
Non consultabile
Data di rilascio
11/12/2026
Riassunto
Amphiphilic copolymers were synthesized through copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) or tri(ethylene glycol) methyl ether methacrylate (TEGMA) as hydrophilic monomers and perfluorohexylethyl acrylate (FA) as hydrophobic comonomer. The copolymerization was carried out by ARGET-ATRP, an advanced radical polymerization technique, that allowed the control over structural parameters such as composition and molecular weight of the final products. The ability of copolymers to self-assemble in solution, with particular reference to a selective solvent as water in PBS solutions, was investigated through dynamic light scattering (DLS) as a function of temperature. At room temperature, these measurements evidenced the presence of small nanoassemblies with hydrodynamic diameter Dh = 7 – 15 nm, compatible with the formation of unimer micelles as already reported in literature for structurally similar amphiphilic copolymers. DLS data were supplemented with DOSY NMR technique, through which, at room temperature, a hydrodynamic radius in agreement to that obtained through DLS measurements was obtained. On heating above a critical temperature, identified as the cloud point temperature (TCp) by light transmittance measurements, multi-chain assemblies were formed with much larger Dh, showing a LCST-type thermoresponsive transition fully and sharply reversible.
The potential use of unimer micelles for the encapsulation of highly hydrophobic drugs, such as Combretastatin A-4 (CA-4), an anticancer drug, was investigated. The encapsulation efficiency was found to be very high (91-95%) for both the investigated copolymers with a polymer/drug ratio of 19/1 in the formulation. The drug release kinetics, evaluated in PBS aqueous solutions, presented similar profiles for both copolymer formulations, being characterized by a linear trend up to ~10 h and then a plateau at around 80% of drug release. In any case, the release rate of CA-4 was slower when incorporated in the unimer micelles in comparison to free, i.e. non-encapsulated, system. The incorporation of CA-4 was found to affect the thermoresponsiveness of the relative copolymer causing a significant reduction in the TCp, which decreased by increasing the amount of drug, with respect to the TCp of the copolymers alone. Cytotoxicity tests were carried out to evaluate the effectiveness of the anticancer drug even when encapsulated. Drug/polymer systems exhibited a similar IC50 with respect to that of non-encapsulated CA-4 against human pancreatic and ovarian tumor cell lines. Finally, the covalent anchorage of a fluorescent comonomer, such as fluorescein O-methacrylate, in a very low percentage (2 mol%), enabled the use of such amphiphilic copolymers as fluorescent probes, allowing the observation of copolymer internalization in the human pancreatic cell line through fluorescent microscopy.
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