Polyoxazolines based lipid nanocapsules for topical delivery of antioxidants

• Published in: International journal of pharmaceutics Vol. 579; p. 119126
• Main Authors: Simon, L., Lapinte, V., Lionnard, L., Marcotte, N., Morille, M., Aouacheria, A., Kissa, K., Devoisselle, J.M., Bégu, S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2020; Elsevier
• Subjects: 3T3 Cells; Animals; Antioxidant; Antioxidants - administration & dosage; Biochemistry; Biochemistry, Molecular Biology; Bioinformatics; Biotechnology; Cancer; Cellular Biology; Computer Science; Drug Carriers - chemistry; Drug Compounding - methods; Genomics; Humans; Immunology; Immunotherapy; Keratinocytes - drug effects; Keratinocytes - radiation effects; Life Sciences; Lipid nanocapsules; Mice; Molecular biology; Nanocapsules - chemistry; Oxazoles - chemistry; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; PEG free; Phospholipids - chemistry; Polyoxazolines; Quercetin - administration & dosage; Reproductive Biology; Sexual reproduction; Skin protection; Subcellular Processes; tert-Butylhydroperoxide - toxicity; Topical delivery; Ultraviolet Rays - adverse effects; HPH; Polyoxazolines; Topical delivery; DL; PIT; Antioxidant; Lipid nanocapsules; PEG free; Skin protection
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119126

[Display omitted] •Innovative PEG free lipid nanocapsules made of an oily core surrounded by a phospholipid and polyoxazoline shell.•Stable nanoformulations loaded with quercetin, a natural antioxidant.•Lipid nanocapsules stabilized by polyoxazoline successfully led to higher drug loading than the original one with PEG.•Powerful antioxidant activity of polyoxazoline based lipid nanocapsules on human keratinocytes after UV exposure. 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 ~30 nm 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.