title: Poly(glycerol methacrylate)-based degradable nanoparticles for delivery of small interfering RNA.
abstract: Nucleic acids therapeutic efficiency is generally limited by their low stability and intracellular bioavailability, and by the toxicity of the carriers used to deliver them to the target sites. Aminated poly(glycerol methacrylate) polymers are biodegradable and pH-sensitive polymers that have been used previously to deliver antisense oligonucleotide and show high transfection efficiency. The purpose of this study is to compare the efficiency and toxicity of aminated linear poly(glycerol methacrylate) (ALT) biodegradable polymer to the most commonly used cationic degradable (i.e. chitosan) and non-degradable (i.e. polyethylenimine (PEI)) polymers for delivery of short interfering RNA (siRNA). ALT, PEI and chitosan polymers were able to form nanosized particles with siRNA. Size, size-distribution and zeta-potential were measured over a wide range of nitrogen-to-phosphate (N/P) ratios, and the stability of the formed nanoparticles in saline and upon freeze-drying was also assessed. No significant cytotoxicity at the range of the tested concentrations of ALT and chitosan nanoparticles was observed, whereas the non-degradable PEI showed significant toxicity in huh-7 hepatocyte-derived carcinoma cell line. The safety profiles of the degradable polymers (ALT and chitosan) over non-degradable PEI were demonstrated in vitro and in vivo. In addition, ALT nanoparticles were able to deliver siRNA in vivo with significantly higher efficiency than chitosan nanoparticles. The results in the present study give evidence of the great implications of ALT nanoparticles in biomedical applications due to their biocompatibility, low cytotoxicity, high stability and simple preparation method.
authors.affiliation: a Assiut International Center of Nanomedicine , Al-Rajhy Liver Hospital, Assiut University , Assiut , Egypt.
authors.forename: Noha G
authors.initials: NG
authors.lastname: Morsi
authors.affiliation: a Assiut International Center of Nanomedicine , Al-Rajhy Liver Hospital, Assiut University , Assiut , Egypt.
authors.forename: Shimaa M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: a Assiut International Center of Nanomedicine , Al-Rajhy Liver Hospital, Assiut University , Assiut , Egypt.
authors.forename: Sherouk S
authors.initials: SS
authors.lastname: Elsonbaty
authors.affiliation: a Assiut International Center of Nanomedicine , Al-Rajhy Liver Hospital, Assiut University , Assiut , Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Afifi
authors.affiliation: b Department of Surgery, Faculty of Medicine , Assiut University , Assiut , Egypt.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Hamad
authors.affiliation: c School of Chemistry and Chemical Engineering , Tianjin University of Technology , Tianjin , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: a Assiut International Center of Nanomedicine , Al-Rajhy Liver Hospital, Assiut University , Assiut , Egypt.|d Laboratory for Synthetic-Biologic Interactions, Department of Chemistry , Texas A&M University , College Station , TX , USA.|e Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.|f Misr University for Science and Technology , 6th of October City , Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Elsabahy
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D011108:Polymers; D034741:RNA, Small Interfering; C043941:polyglycerol; D011094:Polyethyleneimine; D005990:Glycerol
keywords: Biodegradable nanoparticles; chitosan; poly(glycerol methacrylate); polyethylenimine; siRNA