Amphiphilic star-shaped block copolymers as unimolecular drug delivery systems: investigations using a novel fungicide

Abstract

Amphiphilic star-shaped poly(3-caprolactone)-block-poly(oligo(ethylene glycol)methacrylate) [PCL a -b-POEGMA b ] 4 block copolymers with four arms and varying degrees of polymerization for the core (PCL) and the shell (POEGMA) were used to investigate the solution behavior in dilute aqueous solution using a variety of techniques, including fluorescence and UV/Vis spectroscopy, dynamic light scattering, analytical ultracentrifugation, and isothermal titration calorimetry. Particular emphasis has been applied to prove that the systems form unimolecular micelles for different hydrophilic/lipophilic balances of the employed materials. In vitro cytotoxicity and hemocompatibility have further been investigated to probe the suitability of these structures for in vivo applications. A novel fungicide was included into the hydrophobic core in aqueous media to test their potential as drug delivery systems. After loading, the materials have been shown to release the drug and to provoke therewith an inhibition of the growth of different fungal strains.

Synthesis and Solution Properties of Double Hydrophilic Poly(ethylene oxide)-block-poly(2-ethyl-2-oxazoline) (PEO-b-PEtOx) Star Block Copolymers

“…At this point, we assume that this turbidity originates from the aggregation of the star-shaped block copolymers, although both blocks are of hydrophilic nature. Such behavior has also been described for water-soluble homo-and block copolymers in the literature [12,19,[56][57][58]. In some cases, the unexpected aggregation of double-hydrophilic block copolymers was explained by slight differences in the hydrophilicity of both blocks [50,58].…”

“…The "load" can be encapsulated into the inner part (core, hydrophobic) of the materials, while the outer shell (hydrophilic) stabilizes the system in, e.g., aqueous solution [19]. If poly(ethylene oxide) (PEO) is used as the shell, "stealth"-behavior can be observed, also known as "PEGylation", preventing the recognition of such materials by our immune system.…”

“…Regarding the core block, PEO-based materials of different architectures have been thoroughly investigated concerning solution behavior [35,36] or the possibility of being scaffolds in medical applications [19,20,22]. The outer block, poly(2-ethyl-2-oxazoline) (PEtOx), is water-soluble and non-toxic, and the pseudo-peptide character of this material has been shown to induce similar "stealth" behavior, as observed for PEO [19,22,[37][38][39]. PEtOx can be synthesized with a wide range of functional groups, being present via cationic ring-opening polymerization (CROP) [40][41][42][43].…”

Amphiphilic core cross-linked star polymers as water-soluble, biocompatible and biodegradable unimolecular carriers for hydrophobic drugs

“…35,36 In the first step, ROP of CL was initiated from the hydroxyl end group of MeO-PEG-OH, in the presence of the organic catalyst methane sulfonic acid (MSA, CH 3 SO 3 H). 22,39 It is also noteworthy that the use of the organic catalyst MSA rather than a traditional metal catalyst (e.g., tin octoate) favours the synthesis of CCS polymers with narrow polydispersity in high yields and at fast reaction rates, without generation of star-star coupled side-products. BOD was chosen as the degradable cross-linker due to its structural similarity to CL such that the core of the star polymer would chemically resemble PCL only with bridges between the pentylene moieties.…”

“…6,7,[22][23][24][31][32][33][34] Thus, to the best of our knowledge, the CCS polymers reported herein are the first PEG-PCLbased, fully water-soluble, amphiphilic CCS polymers applied as unimolecular drug containers. The key building blocks constituting the CCS polymer are poly(ethylene glycol) (PEG) as the hydrophilic outer shell and bio-degradable poly(ε-caprolactone) (PCL) as the hydrophobic drug-loading compartment.…”