Zeibun Ramtoola, Azeema Moollan, Aisling O’Donnell, Ritesh M. Pabari, Dermot Cox and Brian Kirby

Program Director, MSc Industrial Pharmaceutical Science, School of Pharmacy, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland

Abstract:

Drug delivery to the central nervous system (CNS) remains a challenge due to the difficulty in facilitating drug transport across the blood-brain barrier (BBB). Various types of nanoparticle (NPs) have been investigated and shown to enhance drug delivery and targeting to various cells and tissues including the CNS [1].

The aim of this study was to investigate the potential of NPs of poly-lactide-co-glycolide (PLGA) modified with the cell penetrating peptide, octa-arginine (R8) to enhance drug delivery to the CNS.

NPs containing coumarin-6 or loperamide were prepared using an emulsion solvent evaporation method [2] and were conjugated with R8 at increasing concentration of 2.5, 5 and 10μM. NPs formulated had an average size of 198 to 356nm. Both size and Zeta potential increased when R8 was conjugated to NP surface. NPs were incubated with MDCK cell monolayers, an in vitro BBB model, over 4 hours. R8-PLGA NPs showed enhanced cellular uptake and permeability across the monolayers compared to PLGA NPs as measured by flow cytometry, fluorimetry and confocal microscopy.  When administered intranasally to an in vivo mouse model, delivery of loperamide to the brain was observed for the R8-PLGA NPS, as demonstrated by the increase in latency of the mice to jump or lick a hind paw when placed on the hot plate. The data from this study supports R8-PLGA NP as a potential drug delivery carrier to the brain.

References

[1]        Tosi G., Costantino L., Ruozi B., Forni F., Vandelli M.A. Expert Opinion Drug Delivery. 2008;5(2) 155-74.
[2]        Ramtoola Z et al. J Pharm Pharmacol. 2011 Jan;63(1):26-32