Development of bioadhesive amino-pegylated poly(anhydride) nanoparticles designed for oral DNA delivery.
Amino-pegylated poly(methyl vinyl ether-co-maleic anhydride) nanoparticles were prepared applying a solvent displacement method. The surface charge of the resulting pegylated particles was considerably higher (-2.7 mV) than that of the non-pegylated (-33.5 mV). After oral administration to rats the amino-pegylated nanoparticles exhibited great ability for bioadhesive interactions with the gastrointestinal mucosa. Furthermore, fluorescence microscopy revealed that the amino-pegylated were able to cross the cellular membrane of the absorptive enterocytes. Genomic salmon testes DNA was associated to the amino-pegylated poly(anhydride) particles by applying two procedures: (i) incubation of aqueous DNA solution with the freshly formed amino-pegylated particles; and (ii) initial incubation of DNA and DAP-PEG simultaneously, followed by blending with preformed non-pegylated particles. Gel electrophoresis showed that both methods were safe and DNA integrity was not affected. Based on the results describing their adhesive properties and intracellular transport, the amino-pegylated nanoparticles were considered as a suitable carrier for DNA.
Yoncheva
Krassimira
K
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
Centelles
Miguel N
MN
Irache
Juan M
JM
D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D049388:Polyanhydrides / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D049388:Polyanhydrides; D011092:Polyethylene Glycols; D004247:DNA