Nano-Assemblies from Amphiphilic PnBA-b-POEGA Copolymers as Drug Nanocarriers

Abstract

The focus of this study is the development of highly stable losartan potassium (LSR) polymeric nanocarriers. Two novel amphiphilic poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) copolymers with different molecular weight (Mw) of PnBA are synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, followed by the encapsulation of LSR into both PnBA-b-POEGA micelles. Based on dynamic light scattering (DLS), the PnBA30-b-POEGA70 and PnBA27-b-POEGA73 (where the subscripts denote wt.% composition of the components) copolymers formed micelles of 10 nm and 24 nm in water. The LSR-loaded PnBA-b-POEGA nanocarriers presented increased size and greater mass nanostructures compared to empty micelles, implying the successful loading of LSR into the inner hydrophobic domains. A thorough NMR (nuclear magnetic resonance) characterization of the LSR-loaded PnBA-b-POEGA nanocarriers was conducted. Strong intermolecular interactions between the biphenyl ring and the butyl chain of LSR with the methylene signals of PnBA were evidenced by 2D-NOESY experiments. The highest hydrophobicity of the PnBA27-b-POEGA73 micelles contributed to an efficient encapsulation of LSR into the micelles exhibiting a greater value of %EE compared to PnBA30-b-POEGA70 + 50% LSR nanocarriers. Ultrasound release profiles of LSR signified that a great amount of the encapsulated LSR is strongly attached to both PnBA30-b-POEGA70 and PnBA27-b-POEGA73 micelles.

Micellar drug delivery vehicles formed from amphiphilic block copolymers bearing photo-cross-linkable cyclopentenone side groups

“…In static light scattering analysis of similar amphiphilic PEG- block -poly alkyl acrylate micelles with comparable molecular weight and micelle size an aggregation number of between 111 and 133 was found. 46,47 Based on the structural similarity, and comparable molecular weight and size of these POEGA block copolymer micelles, a similar aggregation number can be expected for the assemblies described here. For block copolymer POEGA 31 -HB 49 , micelles were also prepared via the nanoprecipitation method for comparative purposes.…”

Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers as Nanocarriers for Losartan: Insights into Drug–Polymer Interactions

“…The 1 H-NMR spectrum for the PMeOxz 72 -grad-PPhOxz 28 + 50% LSR nanocarriers in D 2 O in Figure 7, shows the distinct proton signals of LSR clearly (red letters), corroborating its successful loading in the polymeric nanocarriers. Notably, broader proton signals of the LSR phenyl group arise in positions 8-9 and 10-11, compared to those exhibited in previous studies utilizing different copolymers [45,46], implying stronger hydrophobic interactions between the phenyl group of PMeOxz 72 -grad-PPhOxz 28 and phenyl ring of LSR. The chemical shifts of LSR proton signals in the presence of PMeOxz 72 -grad-PPhOxz 28 nanoassemblies, PnBA 30 -b-POEGA 70 [46] and PEO-b-PCL [45] micelles are gathered in Table 5, reflecting its great molecular flexibility and the different extent of interactions with different copolymers.…”

“…Notably, broader proton signals of the LSR phenyl group arise in positions 8-9 and 10-11, compared to those exhibited in previous studies utilizing different copolymers [45,46], implying stronger hydrophobic interactions between the phenyl group of PMeOxz 72 -grad-PPhOxz 28 and phenyl ring of LSR. The chemical shifts of LSR proton signals in the presence of PMeOxz 72 -grad-PPhOxz 28 nanoassemblies, PnBA 30 -b-POEGA 70 [46] and PEO-b-PCL [45] micelles are gathered in Table 5, reflecting its great molecular flexibility and the different extent of interactions with different copolymers. The internal structure of PMeOxz 72 -grad-PPhOxz 28 GC and LSR moieties was confirmed by 2D-COSY measurements though intramolecular interaction analysis between their segments.…”

“…Nuclear magnetic resonance (NMR) spectroscopy is an alternative, not fully explored characterization technique to illuminate the design and drug encapsulation efficiency of polymeric nanocarriers, by thorough examination of the micelle structure and polymerdrug intermolecular interactions [43,44]. Our previous works underlined the importance of NMR spectroscopy, which was the instrument to prove that the level of interaction between the polymers and the drug influenced the stability, encapsulation efficiency (%EE), and drug release kinetics of the studied systems [45,46].…”

Grafted Copolymer Electrolytes Based on the Poly(acrylic acid-co-oligo ethylene glycol acrylate) (P(AA-co-OEGA)) Ion-Conducting and Mechanically Robust Block

“…A promising comb-like (branched-like) homopolymer electrolyte that combines the grafted architecture and the beneficial characteristics of PEO is the poly­(oligo ethylene glycol methacrylate) (POEGMA). − POEGMA and its acrylic analogue poly­(oligo ethylene glycol acrylate) (POEGA) have the advantage of being biocompatible. As such, they have been employed in drug delivery applications. − Specifically, POEGMA (POEGA) consists of a methyl meth­(acrylate) backbone and ethylene glycol side groups. Despite its rigid backbone, the segmental dynamics and the associated T g are dominated by the EO side chains and are similar to that of PEO .…”