Surface-Engineered Mucus Penetrating Nucleic Acid Delivery Systems with Cell Penetrating Peptides for the Lungs

• DOI: 10.1021/acs.molpharmaceut.1c00770
• Publication Date: 2022-03-25T22:58:44Z
• Authors: Anupama Kumari; Simanti Pal; Betsy Reshma G; Franklin Pulikkot...; Nidhi Gupta; Chirag Miglani; Bijay Pattnaik; Asish Pal; Munia Ganguli
• Keywords: 0301 basic medicine; Drug Carriers; Mucus; 03 medical and health sciences; Nucleic Acids; Mucins; Nanoparticles; Mannitol; Cell-Penetrating Peptides; Lung; 3. Good health

Nucleic acids, both DNA and small RNAs, have emerged as potential therapeutics for the treatment of various lung disorders. However, delivery nucleic acids to lungs is challenging due barrier property imposed by mucus, which further reinforced in disease conditions such chronic obstructive pulmonary asthma. The presence negatively charged mucins imparts electrostatic property, mesh network structure mucus provides steric hindrance system. To overcome this, system either needs be muco-inert with a low positive charge that interactions are minimized or should ability transiently dismantle effective penetration. We developed penetrating RNA plasmid independently. acid core consists (pDNA/siRNA) cationic/amphipathic cell peptide. coating hydrophilic biopolymer chondroitin sulfate A (CS-A) conjugated mucolytic agent, mannitol. hypothesize CS-A would reduce surface decrease interaction mucins, while mannitol residues disrupt mucin–mucin viscosity increasing influx water into mucus. Our results indicate CS-A–mannitol-coated nanocomplexes possess reduced charge, artificial increased diffusion mucin suspension well penetration through layer compared non-coated ones. Further, coated showed cytotoxicity higher transfection A-549 BEAS-2B cells