Preparation and evaluation of double coated poly (Butyl CyanoAcrylate) nanoparticles for brain targeting of D-Kyotorphin via oral administration

The aim of this study is to prepare and evaluate oral administration of poly (butyl cyano acrylate) nanoparticles (PBCA), double-coated with Tween 80 and poly ethylene glycol (PEG) 20,000 for brain delivery of dipeptide D-kyotorphin (D - KTP), an anti-nociceptive peptide that does not cross blood-brain barrier. PBCA nanoparticles were fabricated by anionic polymerization of n-butyl cyano acrylate monomer (1% v/v) containing Dextran 70 (1.5% w/v) as a stabilizer. D - KTP was loaded on porous PBCA nanoparticles by absorption and the surfaces of nanoparticles were successively double-coated with Tween 80 and PEG 20,000 in varied concentrations of up to 2% each. The PBCA nanoparticles had mean particle sizes of approximately 100 nm (polydispersity index 0.025), mean zeta potentials of -17.88 to -2.24 mV and drug loadings of 39% w/w. Results from in vitro release kinetics studies, stability studies in simulated gastric and intestinal fluids indicated that surface coat of PEG inhibited the release of D - KTP and demonstrated better protection of the peptide from gastrointestinal enzymes and pH. Results from the hot plate test carried out in mice indicated that significant D KTP induced analgesia was observed from PBCA nanoparticles with double-coating of Tween and PEG as comparison with single-coating of either Tween or PEG. Hence, we could conclude that surface coated PBCA nanoparticles can be used successfully for brain targeting of D - KTP orally.