Poly Oxazolines Research Articles

Interactions of amphiphilic polyoxazolines formulated or not in lipid nanocapsules with biological systems: Evaluation from membrane models up to in vivo mice epidermis

In this study, we evaluated the potential of amphiphilic polyoxazolines (POx) to interact with biological membranes thanks to models of increasing complexity, from a simple lipid bilayer using giant unilamellar vesicles (GUV), to plasma membranes of three different cell types, fibroblasts, keratinocytes and melanocytes, which are found in human skin. Upon assessing an excellent penetration into GUV membranes and cultured cells, we addressed POx’s potential to penetrate the murine skin within an in vivo model. Exposure studies were made with native POx and with POx encapsulated within lipid nanocapsules (LNC). Our findings indicate that POx’s interactions with membranes tightly depend on the nature of the alkyl chain constituting the POx. Saturated C16POx insert rapidly and efficiently into GUV and plasma membranes, while unsaturated C18:2POx insert to a smaller extent. The high amount of membrane-inserted saturated C16POx impacts cell viability to a greater extent than the unsaturated C18:2POx. The in vivo study, performed on mice, showed an efficient accumulation of both POx types in the stratum corneum barrier, reaching the upper epidermis, independently of POx’s degree of saturation. Furthermore, the formulation of POx into lipid nanocapsules allowed delivering an encapsulated molecule, the quercetin, in the upper epidermis layers of murine skin, proving POx’s efficacy for topical delivery of active molecules. Overall, POx proved to be an excellent choice for topical delivery, which might in turn offer new possibilities for skin treatments in diseases such as psoriasis or melanomas.

Polyoxazolines based lipid nanocapsules for topical delivery of antioxidants.

Nano-sized lipid formulations offer a great potential for topical delivery of active compounds to treat and prevent human skin damages. Of particular importance is the high loading of hydrophobic molecules, the long-term stability and the auspicious penetration capacity especially reached when using lipid nanocapsules (LNC). Unfortunately, their formation currently relies on a phase inversion process that only operates when using a poly(ethylene glycol) (PEG) based surfactant belonging to the controversial PEG family that was subject of clinical awareness. The present study proposes an alternative to this overused polymer in formulations by designing LNC made of harmless amphiphilic polyoxazolines (POx). Implementing a short sonication step in the process allowed well-defined spherical nanoparticles of ~30nm to be obtained. The structure of the so called LNC POx was composed of an oily core surrounded by a rigid shell of phospholipids and POx, which ensures a high stability over time, temperature, centrifugation and freezing. Encapsulation of the natural quercetin antioxidant led to a drug loading three times higher than for LNC constituted of PEG (LNC PEG). The antioxidant activity of loaded LNC POx was tested on mice fibroblasts and human keratinocytes after exposure to free radicals from peroxides and UVB irradiation, respectively. The radical scavenging capacity of quercetin loaded in the LNC POx was preserved and even slightly enhanced compared to LNC PEG, highlighting the POx value in nanoformulations.

Polyoxazolines based mixed micelles as PEG free formulations for an effective quercetin antioxidant topical delivery.

This study aims to prove the value of the polyoxazolines polymer family as surfactant in formulations for topical application and as an alternative to PEG overuse. The amphiphilic polyoxazolines (POx) were demonstrated to have less impact on cell viability of mice fibroblasts (NIH3T3) than their PEG counterparts. Mixed micelles, made of POx and phosphatidylcholine, were manufactured using thin film and high pressure homogenizer process. The mixed micelles were optimized to produce nanosized vesicles of about 20 nm with a spherical shape and stable over 28 days. The natural lipophilic antioxidant, quercetin, was successfully encapsulated (encapsulation efficiency 94 ± 4% and drug loading 3.6 ± 0.2%) in the mixed micelles with no morphological variation. Once loaded in the formulation, the quercetin impact on cell viability of NIH3T3 was decreased while its antioxidant activity remained unchanged. This work highlights the capacity of amphiphilic POx to create, in association with phospholipids, stable nanoformulations which show promise for topical delivery of antioxidant and ensure skin protection against oxidative stress.

Development of Cancer-Targeted Single Photon Emission Computed Tomography/Fluorescence Dual Imaging Probe Based on Polyoxazoline

Polyoxazolines (POZs) are biocompatible hydrophilic polymers composed of N-acylethylenimine. Our previous study showed that many fluorescence dyes could be introduced into the secondary amino group...

How to Modulate the Chemical Structure of Polyoxazolines by Appropriate Functionalization

Polyoxazolines (POx) are increasingly being studied as polymeric building blocks due to the possibility of affording tunable properties. Additionally, as the biocompatibility and stealth behavior of POx are similar to that of poly(ethylene glycol) (PEG), it has become challenging to develop polyoxazoline-based (co)polymers. Even if POx have a lot of advantages, they also show an important drawback, as it has been impossible, to date, to prepare high-molecular-weight polyoxazolines with a low polydispersity index. Thus, it appears important that they be judiciously functionalized. This review covers the multiple ways that polyoxazolines can be functionalized. The use of functional initiators, functional terminating agents, and 2-R-2-oxazolines with an R functional side group is detailed. In conclusion, some perspectives on POx functionalizations are also reported, with functions permitting selective "click" reactions.

Novel initiators for oxazoline polymerization: generation of polydiacetylene-polyoxazoline networks

A series of bolaform polyoxazolines (POZO) with 1,3-diacetylene cores ((POZO)m-(CH2)n-C≡C-C≡C-(CH2)n-(POZO)m) were synthesized by the living polymerization of 2-methyl-1,3-oxazolines initiated by triflate esters derived from bis(ω-hydroxyalkyl)-1,3-diacetylenes. The chain length of the alkylspacers within the diacetylene core as well as the length of the attached polyoxazoline chains was varied between n = 1 and 4; m = 5, 10 and 15. The thermally induced 1,4-addition process yielding polydiacetylenes (PDA) was studied leading to highly conjugated POZO-PDA hybrid materials.