NOVEL SELF-ASSEMBLY NANOCARRIERS STABILIZED BY DRUG-COMPATIBLE CHEMISTRIES

Polymeric micelles (PMs) are self-assembly nanocarriers formed by amphiphilic block copolymers above the so-called critical micellar concentration (CMC). Clinical studies with PMs were conducted only for the intravenous chemotherapy of cancer. Only a few attempts have been made to assess their clinical performance by minimally-invasive routes. PMs with optimal performance in mucosal administration should be mucoadhesive, display high physical stability under dilution and sustain the release of the cargo. This work investigated the design of a novel kind of nanocarrier based on the micellization of thermo-responsive copolymers synthesized by the grafting of oligo(N-isopropylacrylamide) (oligo(NiPAam)) blocks to mucoadhesive polyol templates (e.g., chitosan (CS), poly(vinyl alcohol) (PVA)), their micellization and the later crosslinking of the hydrophilic corona with tripolyphosphate (TPP) and boric acid (BA), respectively. Graft copolymers were synthesized by free radical polymerization of NiPAam and characterized by ¹H-NMR, FTIR, elemental analysis, GPC and DSC. The CMC, the size, size distribution and Z-potential were studied by DLS and the concentration by Nanoparticle Tracking Analysis (NTA). The morphology and nanostructure of the micelles was investigated by cryoTEM, the mucoadhesion by the mucin solution method (DLS and NTA) and the cytocompatibility and cell uptake in Caco2 cell monolayers. Finally, the encapsulation of these micelles was evaluated with efavirenz. One percent PMs increased the solubility of the drug from 7 microg/mL to 1.2 mg/mL, a performance that could be improved by increasing the hydrophobicity of the hydrophobic blocks. Overall results support the potential of these nanocarriers for improved mucosal administration of prophylactic and therapeutic agents.

Acknowledgements: This work is supported by the European Union`s - Seventh Framework Programme under grant agreement #612675-MC-NANOTAR.