From nanospheres to micelles: simple control of PCL-g-PEG copolymers’ amphiphilicity through thiol–yne photografting

Abstract

A simple method for the synthesis of a family of poly(ɛ-caprolactone)-g-polyethylene glycol (PCL-g-PEG) copolymers of controlled amphiphilicity and their use to generate nanospheres or micelles are reported. PCL-g-PEG with various compositions are prepared from a single strategy relying on a combination of post-polymerization modification and subsequent thiol-yne photografting. Alkyne-functional PCL (PCL-yne) are first obtained by anionic activation and reaction with propargyl bromide to yield PCL-yne with 8% alkyne groups. PEG-thiol is then reacted on PCL-yne under UV activation to yield the targeted graft copolymer by thiol-yne photoaddition. The advantage of the approach is that control over the composition is easily achieved yielding to amphiphilic graft copolymers with ethylene glycol/ caprolactone (EG/CL) ratios ranging from 0.1 to 1.3. Starting from this single strategy, it was therefore possible to obtain nanospheres (D H~5 5 nm) or micelles (D H~3 0 nm) by copolymers self-assembly depending on the ratio EG/CL. The potential of the PCL-g-PEG micelles as drug carrier was finally evaluated with curcumin that was efficiently encapsulated, protected and released over 80 days. Interestingly it was found that drug encapsulation efficiency and drug loading were higher for PCL-g-PEG copolymers compared to block PCL-b-PEG.

PCL–PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems

“…The PCL-yne/PEG-SH reactions were performed according to our previous work. 36 In a typical experiment, PCL-yne (100 mg; 8% alkyne groups with respect to CL units, M n ¼ 21 300 g mol À1 ; Ð = 2.4); and PEG2k-SH (820 mg; 6 eq. with respect to the alkyne group) were dissolved in DMF (10 mL) in a Schlenk flask ( Table 1, entry 2).…”

“…Blank and drug loaded PCL-g-PEG nanoaggregates were prepared by the self-assembly method according to our previous article. 36 Typically, the drug (5 mg) and PCL-g-PEG (35 mg) were dissolved in 2 mL acetone. Then 5 mL of PBS were added.…”

“…The prepared PCL-g-PEG polymers with EG/CL ratios ranging from 0.1 to 1.3 formed nanoparticles and frozen micelles of different hydrodynamic diameters. 36 The hydrophilicity of the previously prepared systems was however quite low, resulting in PEGylated nanoparticles with low PEG density rather than micelle-like nanoaggregates, which may limit the release properties. In addition, the impact of the copolymer hydrophilic/hydrophobic balance on the ability to deliver various drugs was not investigated.…”

Novel amphiphilic temperature responsive graft copolymers PCL-g-P(MEO2MA-co-OEGMA) via a combination of ROP and ATRP: synthesis, characterization, and sol-gel transition

“…According to the literatures [34][35][36][37][38], functional PCL have been widely reported which prepared by homopolymerization or copolymerization with ε-caprolactone (CL) and ε-caprolactone derivatives. They allowed the active group to attach on the PCL side groups, which could introduce side-chain of different properties to construct functional graft copolymers to improve its insufficient, such as mPEG-b-(PCL-g-PMAA) [35], PCL-g-PDMAEMA [36,37], PCL-g-PHEMA [38], PCL-g-PMMA [39], PCL-g-PEG [34,40]. PEG or PEO grafted copolymers can offer more versatility and latitude as the hydrophilicity of the polymers can be modulated by both the length and graft numbers of hydrophilic segment, whereas the responsive temperature of graft copolymers could hardly be modulated.…”

Synthesis of three-dimensional porous hyper-crosslinked polymers via thiol–yne reaction

“…Herein we present the synthesis of porous, three-dimensional tetraphenylmethane-based networks by another click reaction, the thiol–yne reaction [14–19]. This reaction type has been known for several decades and relived a renaissance in the past decade, especially in material sciences [20–32], due to its mild, and metal-free reaction conditions, high yields and easy purification.…”