Delivery of analgesic peptides to the brain by nano-sized bolaamphiphilic vesicles made of monolayer membranes

Mary Popov, Ibrahim Abu Hammad, Tzach Bachar, Sarina Grinberg, Charles Linder, David Stepensky, Eliahu Heldman

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Inefficient drug delivery to the brain is a major obstacle for pharmacological management of brain diseases. We investigated the ability of bolavesicles - monolayer membrane vesicles self-assembled from synthetic bolaamphiphiles that contain two hydrophilic head groups at each end of a hydrophobic alkyl chain - to permeate the blood-brain barrier and to deliver the encapsulated materials into the brain. Cationic vesicles with encapsulated kyotorphin and leu-enkephalin (analgesic peptides) were prepared from the bolalipids GLH-19 and GLH-20 and studied for their analgesic effects in vivo in experimental mice. The objectives were to determine: (a) whether bolavesicles can efficiently encapsulate analgesic peptides, (b) whether bolavesicles can deliver these peptides to the brain in quantities sufficient for substantial analgesic effect, and to identify the bolavesicle formulation/s that provides the highest analgetic efficiency. The results indicate that the investigated bolavesicles can deliver analgesic peptides across the blood-brain barrier and release them in the brain in quantities sufficient to elicit efficient and prolonged analgesic activity. The analgesic effect is enhanced by using bolavesicles made from a mixture the bolas GLH-19 (that contains non-hydrolyzable acetylcholine head group) and GLH-20 (that contains hydrolysable acetylcholine head group) and by incorporating chitosan pendants into the formulation. The release of the encapsulated materials (the analgesic peptides kyotorphin and leu-enkephalin) appears to be dependent on the choline esterase (ChE) activity in the brain vs. other organs and tissues. Pretreatment of experimental animals with pyridostigmine (the BBB-impermeable ChE inhibitor) enhances the analgesic effects of the studied formulations. The developed formulations and the approach for their controlled decapsulation can serve as a useful modality for brain delivery of therapeutically-active compounds.

Original languageEnglish
Pages (from-to)381-389
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3 PART A
StatePublished - 1 Jan 2013


  • Analgesic peptides
  • Bolavesicles
  • Brain delivery of drugs
  • Drug delivery systems
  • Liposomes

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science


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