"Grafting-from" synthesis and characterization of poly (2-ethyl-2-oxazoline)-b-poly (benzyl L-glutamate) micellar nanoparticles for potential biomedical applications

Abstract

Introduction: Recent advances in the field of poly (2-oxazolines) as bio-inspired synthetic pseudopeptides have proven their potential biomedical applications such as drug delivery and tissue engineering. Methods: In order to fabricate a biodegradable micellar nanoparticle of poly (2-ethyl 2-oxazoline)-b-poly (benzyl L-glutamate) or pEOx-b-pBLG, "grafting-from" synthesis approach was used involving consecutive steps of cationic ring-opening polymerization of 2-ethyl-2-oxazoline, amine functionalization of pEOx using 1-Boc-piperazine and N-carboxyanhydride polymerization of γ-benzyl- L-glutamate. Following hydrolysis of the copolymer, the protecting γ-benzyl groups were removed yielding a double-hydrophilic block ionomer of pEOx-b-poly (L-glutamic acid). The polymers were characterized by FTIR, 1H-NMR, size exclusion chromatography and differential scanning calorimetry (DSC). Aqueous assembly of the polymers was investigated by pyrene assay, dynamic light scattering, and transmission electron microscopy. MTT cytotoxicity assay was also performed to determine the cytocompatibility in various tumor cell lines. Results: The polymeric micelles presented a uni-modal size distribution with mean hydrodynamic diameter of 149.8 ± 10.6 nm and critical aggregation concentration of 60 µg/mL. The average molecular weight of pEOx increased from ~ 14 to 20 kDa for pEOx-b-poly (L-glutamic acid) as determined by light scattering (Debye plot), indicating a successful copolymerization. MTT assay showed little to no practical cytotoxicity at concentrations below 1 mg/mL. Conclusion: Multi-step synthesis of pEOx-b-pBLG and subsequent alkaline hydrolysis were performed to obtain the block ionomer pEOx-b-poly (L-glutamic acid). Both pEOx-based copolymers can be considered for various potential applications such as loading and delivery of drugs, genes, and contrast agents either by chemical conjugation or physical loading.

Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma

“…To estimate CMC values of the synthesized lipopolymers, the pyrene assay was performed. 13 , 40 Briefly, 25 µL of pyrene solution (4 µg/µL in acetone) was transferred into microtubes and dried overnight under chemistry cabinet. One mL of each lipopolymer dispersion prepared at various concentrations (0.001, 0.005, 0.01, 0.05, 0.1, and 1 mg/mL) were added and stirred at 800 rpm for 24 hours.…”

“…Among various nano-sized drug delivery systems intended to improve physicochemical (solubility) and pharmacokinetic characteristics of the drug, self-assemblies of amphiphilic polymers contain a hydrophobic inner core that provides the ability to dissolve hydrophobic drugs and a hydrophilic shell which grants the carrier stability in water. 10 - 13 Polymeric self-assembled nanoparticles offer several advantages such as high kinetic and thermodynamic stability, suitable size (20–100 nm), narrow size distribution, easily adjustable surface potential, modulated biocompatibility, tissue accumulation and penetration, controlled intracellular trafficking, controlled release, and reduced inherent toxicity. 14 , 15 Notably, there are crucial factors in the design of nanoparticles including morphology (size and shape) and surface characteristics that can influence on both pharmacokinetics and cell uptake.…”

Microwave-assisted rapid synthesis of chiral oxazolines

“…Therefore, the electron donor group might have a potential inhibitory effect on the reactivity of aryl benzonitrile, and electron-withdrawing groups might promote the reaction of the substrate and activate cyano groups. Moreover, different substitution sites of electron-withdrawing groups might also lead to great differences in yields (5)(6)(7)(8)(9)(10)(11). The electron-withdrawing group had the best reactivity in the meta-position (5), and the product could only be obtained in a general yield (6) when it was in the ortho-position and in a good yield in the para-position (7).…”

“…5 In addition to drug discovery, 2-oxazolines are also reported in the field of materials science such as nanomaterials. [6][7][8][9][10][11] On the other hand, chiral 2-oxazoline compounds are commonly used ligands in metal-catalyzed asymmetric synthesis. [12][13][14] The oxygen and nitrogen atoms of chiral oxazolines exhibit suitable affinity for various metal ions in a bidentate chelation mode.…”

The Synergistic Effect of Biochar and Poly(2-ethyl-2-oxazoline)/poly(2- hydroxyethylmethacarylate)/Chitosan) Hydrogels on Saline Soil Properties and Carrot Productivity

“…The peak of CH 3 appears at 1381 cm − 1 [44].The full spectrum of PEtOx exposes that the appearance of an overlapping peak at 1640 cm − 1 due to the presence of amide carbonyl bonds. Furthermore, the respective strong double peaks at 2874, 2933 and 2974 are attributed to alkane -CH 2 -stretching and bending groups [45,46]. The OH bonding at 3484 cm − 1 on the PEtOx hydrogel was attributed to the hydroxyl terminated feature of the hydrogel [47].…”