Synthesis and micellization of thermosensitive PNIPAAm-b-PLA amphiphilic block copolymers based on a bifunctional initiator

Abstract

The thermo-sensitive amphiphilic block copolymer poly(N-isopropylacrylamide)-block-poly(D,L-lactide) (PNIPAAm-b-PLA) was synthesized using a simple free radical copolymerization route based on a bifunctional initiator, 2,2-azobis(2-methylpropion amidine) dihydrochloride followed by the ring-opening polymerization of D,L-actide in the presence of a Sn(Oct) 2 catalyst. The chemical structure of the PNIPAAm-b-PLA copolymers was verified using Fourier transform-infrared spectrophotometry and nuclear magnetic resonance, and the molecular weight and polydispersity index were examined using gel permeation chromatography. The amphiphilic PNIPAAm-b-PLA block copolymers could self-assemble into spherically shaped micelles in an aqueous solution with a transmission electron microscopy diameter range of 40-56 nm and a dynamic laser scattering hydrodynamic diameter of 90-200 nm. This behavior depends on the environmental temperature, the hydrophobic interactions among PNIPAAm molecular chains, the intermolecular hydrogen bonding between the PNIPAAm chains and water molecules, and the intramolecular hydrogen bonding between the -CONH 2 groups. The copolymers held a critical micellization concentration of 4.93-7.21 mg·L -1 and a low critical solution temperature of 31.15-32.62 o C being more or less affected by their compositions, PLA or PNIPAAm block length, and polymerization temperature. The as-prepared PNIPAAm-b-PLA block polymers are anticipated to be applied as candidate drug release carriers.

Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin

“…The difference in sizes should be attributed to the fact that the TEM reveals the morphological size of the nanoparticle in the solid state; however zetasizer measure the hydrodynamic diameter of the nanoparticle in aqueous solutions. Our results are well in accordance with the previous reports [48,49]. Another reason might be due to the operation principal of both instruments while zetasizer measured the average particle size while TEM measured the size of individual particles.…”

Thermosensitive poly(N-isopropyl acrylamide-co-N,N-dimethyl acryl amide)-block-poly(d,l-lactide) amphiphilic block copolymer micelles for prednisone drug release

“…The synthesis of thermosensitive poly( N -isopropylacrylamide- co - N,N -dimethylacrylamide)-block-poly( D,L -lactide) (P(NIPAM- co -DMAM)- b -PLA) copolymers was achieved using our two-step process. 33 Briefly, NIPAM and DMAM were dissolved in 25 mL THF in line with the mass ratios of NIPAM to DMAM 100/0, 90/10, 80/20, and 70/30. The bifunctional initiator AMAD (2 wt% of the monomers) was introduced, and dried nitrogen was bubbled through the solution for 30 min.…”

“…The –OH chain ends were formed from bifunctional initiator residues according to free radical polymerization mechanism. 33 The Fourier transform infrared spectra (FT-IR): ν (cm −1 ) = 1647 (C═O, amide I), 1546 (–NH, amide II), 3304 and 3430 (–NH and terminal –OH), and 1397 (C–N). 1 H nuclear magnetic resonance (NMR) (300 MHz, CDCl 3 ): δ (ppm) = 2.92 (s, –N( CH 3 ) 2 ), 2.07 (t, – CH –CH 2 – in main repeating units), 1.13 (d, –NHCH( CH 3 ) 2 ), 3.99 (m, –NH CH (CH 3 ) 2 ), 6.65 (m, – NH CH(CH 3 ) 2 ), 4.14 (m, weak, –CONHCH 2 CH 2 OH), 3.64 (m, weak, –CONH CH 2 CH 2 OH), and 2.76 (t, weak, –CH 2 CH 2 OH , –OH end group).…”

Thermosensitive self‐assembly micelles from A2BA2‐type poly(N‐isopropyl acrylamide)2‐b‐Poly(lactic acid)‐b‐Poly(N‐isopropyl acrylamide)2 four‐armed star block copolymers and their applications as drug carriers

“…Poly( N ‐isopropyl acrylamide) (PNIPAM) is an extensively researched thermosensitive polymer drug carrier, which can undergo a sharp phase transition at the so‐called lower critical solution temperature (LCST) of 32–33°C in aqueous media . Various block copolymers containing PNIPAM fragments have been synthesized for biomedical applications . This thermal response can be used to modulate the interactions of the micelles with cells, protein, and other biocomponents, and these copolymers are thus suitable for applications in the medicinal field as carriers of therapeutic and diagnostic drugs and can achieve peculiar targeting in tumor remedies .…”

“…Linear PNIPAM‐ b ‐PLA block copolymers have been studied extensively; they have almost the same LCST values as the PNIPAM homopolymer. Their spontaneous self‐assembly in aqueous solution and their drug loading and release depends on the media temperature, copolymer compositions, PLA and PNIPAM block lengths, hydrophobic interactions among the PNIPAM chains, intermolecular hydrogen bonding between the PNIPAM chains and water molecules, and intramolecular hydrogen bonding between the CONH 2 groups.…”