Formulation, characterization and permeability study of nano particles of lipo-endomorphin-1 for oral delivery

Three different formulations of a lipid-modified endomorphin-1 peptide (C(10)LAA-Endo-1) were prepared, characterized, and evaluated for their permeability through Caco-2 cell membranes. Solid lipid nanoparticles (SLN), enteric coated (EC), and the EC-SLN of C(10)LAA-Endo-1 is a modified structure of endomorphin-1 for oral delivery. Physico-chemical characterization of the formulations showed that among all formulations, EC-[C(10)LAA-Endo-1] had the lowest particle size and the highest EE% and absolute zeta potential. Release of drug from SLN, EC-SLN and EC[ C(10)LAA-Endo-1] in acid media was 14.30 (+/- 2.7)%, 3.0 (+/- 1.0)% and 10.2 (+/- 3.0)%, respectively. Release data in buffer media (pH = 7.4) showed that enteric coated formulations released C(10)LAA-Endo-1 more slowly than uncoated formulations. It was also demonstrated that direct coating of C(10)LAA-Endo-1 with Eudragit (R) S100 significantly enhanced the permeability of the compound through Caco-2 cell membranes with a 39-fold higher P-app compared to C(10)LAA-Endo-1. These findings indicated that EC-C(10)LAA-Endo-1 is a promising candidate to promote the oral delivery of the previously modified endomorphin-1 peptide analogue and is worthy of future animal investigations.