Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes

Abstract

Nanoparticles (NPs) have gained importance in addressing drug delivery challenges across biological barriers. Here, we reformulated pentamidine, a drug used to treat Human African Trypanosomiasis (HAT) in polymer based nanoparticles and liposomes and compared their capability to enhance pentamidine penetration across blood brain barrier (BBB). Size, polydispersity index, zeta potential, morphology, pentamidine loading and drug release profiles were determined by various methods. Cytotoxicity was tested against the immortalized mouse brain endothelioma cells over 96 h. Moreover, cells monolayer integrity and transportation ability were examined for 24 h. Pentamidine-loaded polycaprolactone (PCL) nanoparticles had a mean size of 267.58, PDI of 0.25 and zeta potential of –28.1 mV and pentamidine-loaded liposomes had a mean size of 119.61 nm, PDI of 0.25 and zeta potential 11.78. Pentamidine loading was 0.16 µg/mg (w/w) and 0.17 µg/mg (w/w) in PCL NPs and liposomes respectively. PCL nanoparticles and liposomes released 12.13% and 22.21% of pentamidine respectively after 24 h. Liposomes transported 87% of the dose, PCL NPs 66% of the dose and free pentamidine penetration was 63% of the dose. These results suggest that liposomes are comparatively promising nanocarriers for transportation of pentamidine across BBB.

Keywords:

• Pentamidine
• PCL nanoparticles
• liposomes
• blood brain barrier
• transendothelial electrical resistance
• Human African Trypanosomiasis

Acknowledgements

The authors would like to thank the UWC, South Africa and particularly the Schools of Pharmacy and Life Sciences for provision of facilities and laboratory space for carrying out this research. Furthermore, authors extend thanks to Dr. Cummings and Mr. Earl from the School of Physics for helping the morphological characterization of nanoparticles and liposomes by SEM. We also thank NMAIST for providing permission to undertake this study at the UWC. GO acknowledges the Tanzanian Higher Education Students’ Loan Board (HESLB) and NMAIST CREATES Program for providing financial support that enabled undertaking of this project.

Disclosure of interest

The authors report no conflict of interest.