Co-Encapsulation and Co-Delivery of Peptide Drugs via Polymeric Nanoparticles.


Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. [Email]


Combination therapy is a promising form of treatment. In particular, co-treatment of P3 and QBP1 has been shown to enhance therapeutic effect in vivo in treating polyglutamine diseases. These peptide drugs, however, face challenges in clinical administration due to poor stability, inability to reach intracellular targets, and lack of method to co-deliver both drugs. Here we demonstrate two methods of co-encapsulating the peptide drugs via polymer poly(ethylene glycol)-block-polycaprolactone (PEG-b-PCL) based nanoparticles. Nanoparticles made by double emulsion were 100⁻200 nm in diameter, with drug encapsulation efficiency of around 30%. Nanoparticles made by nanoprecipitation with lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) were around 250⁻300 nm in diameter, with encapsulation efficiency of 85⁻100%. Particles made with both formulations showed cellular uptake when decorated with a mixture of peptide ligands that facilitate endocytosis. In vitro assay showed that nanoparticles could deliver bioactive peptides and encapsulation by double emulsion were found to be more effective in rescuing cells from polyglutamine-induced toxicity.


co-delivery,co-encapsulation,double emulsion-solvent evaporation technique(s),nanoparticles,peptide delivery,polymeric drug delivery system,

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