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  • Title: Protein-bearing cubosomes prepared by liquid precursor dilution: inner ear delivery and pharmacokinetic study following intratympanic administration.
    Author: Liu H, Wang Y, Wang Q, Li Z, Zhou Y, Zhang Y, Li S.
    Journal: J Biomed Nanotechnol; 2013 Oct; 9(10):1784-93. PubMed ID: 24015508.
    Abstract:
    This study aims to design self-assembled cubic liquid crystalline nanoparticles (cubosomes) to enhance inner ear bioavailability of earthworm fibrinolytic enzyme (EFE). The cubosomes were prepared using a liquid precursor mixture containing glyceryl monooleate, hydrotrope propylene glycol, and F127 as stabilizer. Submicron-size particles (100 nm to 200 nm) with slight negative charge formed spontaneouly upon dilution of the liquid precursors. Small-angle X-ray scattering (SAXS) results demonstrated that the formation of cubsomses largely depended on the hydration level of liquid precursor and the encapsulation of highly hydrophilic EFE induced the phase transition of the cubosome. The encapsulatoin efficiency of EFE in cubosomes was 79.6% and their cubic ultrastructure were confirmed by TEM. In vitro cell toxicity results showed that the viability of L929 cells decreased by increasing the concentration of nanoparticles. Octadecyl rhodamine B chloride (R18) labeled cubosomes were identified in the basal turn of the scala tympani and middle portion of the cochlea after 30 min post intratympanic administration, indicating that cubosomes could permeate through the RWM. The AUC(0 h-24 h) of EFE administrated as EFE cubosomes was 2.6-fold in cochlear fluid compared to those applied by free drug via the intratympanic route. In conclusion, self-assembled liquid crystalline nanoparticles provide a promising protein vehicle for effective inner ear drug delivery.
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