Lipospheres: Solid Lipid Nanoparticles, opportunities and challenges

Lipospheres are drug loaded solid lipid spheres decorated with phospholipids and surfactants, designed to deliver active agents. Micro and nano size Liposphere, also termed as Solid Lipid Nanoparticles (SLN), were first reported in 1989 in a series of patents and publications [1-4]. Lipospheres were prepared by melt process where the lipid and drug are melted and mixed with hot buffer containing the phospholipids and surfactants and homogenized to form a uniform emulsion that upon rapid cooling forms a dispersion. Alternatively, the drug, lipid, phospholipid and surfactants are dissolved in an organic solvent and evaporated in a large flak to form a thin film. Upon addition of worm buffer and homogenization, a lipid suspension is obtained. Lipospheres were prepared for extended delivery of local anesthetics, vaccines, antibiotics, insect repellent, cosmetic agents and more [5]. An in situ formulation, termed Pro-Nanodispersion Lipospheres (PNL), that spontaneously form nanoparticles upon addition to aqueous media, were invented for the improved oral bioavailability of cyclosporin []. The oily formulation loaded in soft gelatin capsules spontaneously forms lipid nanoparticles of 30 nm upon contact with GI fluids that significantly improved the oral bioavailability of cyslosporin [4]. Similar formulations for improved oral delivery of cannabinoids are under clinical development [6].

Lipospheres, PNL or SLN have potential applications in the delivery of water insoluble active agents by different routes of administration for improved bioavailability. Potential applications out of the medical field will be discussed.

References

1. US5188837A (1989), PCT/US1990/006519, US5188837A
2. Domb AJ. Long-Acting Injectable Oxytetracycline-Liposphere Formulations. International Journal of Pharmaceutics 1995;124(2):271-278.
3. Masters DB, Domb AJ. Liposphere local anesthetic timed-release for perineural site application. Pharmaceutical Research 1998;15(7):1038-1045.
4. Bekerman T, Golenser J, Domb A. Cyclosporin nanoparticulate lipospheres for oral administration. Journal of Pharmaceutical Sciences 2004;93(5):1264-1270.
5. Elgart A, Cherniakova I, Aldouby Y., Domb AJ, Hoffman A, Lipospheres and Pro-Nano Lipospheres for Delivery of Poorly Water Soluble Compounds, Chem. Phys. Lipids, (2012), 165(4), 438-453.
6. I Cherniakov, D Izgelov, D Barasch, E Davidson, AJ Domb, A Hoffman, Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration, J Control Release.2017 Nov 28;266:1-7.