Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS).
The aim of this investigation was to develop and evaluate a novel nanoparticles-in-microsphere oral system (NiMOS) for gene delivery and transfection in specific regions of the gastrointestinal (GI) tract. Plasmid DNA, encoding either for beta-galactosidase (CMV-betagal) or enhanced green fluorescent protein (EFGP-N1), was encapsulated in type B gelatin nanoparticles. NiMOS were prepared by further protecting the DNA-loaded nanoparticles in a poly(epsilon-caprolactone) (PCL) matrix to form microspheres of less than 5.0 microm in diameter. In order to evaluate the biodistribution following oral administration, radiolabeled ((111)In-labeled) gelatin nanoparticles and NiMOS were administered orally to fasted Wistar rats. The results of biodistribution studies showed that, while gelatin nanoparticles traversed through the GI tract fairly quickly with more than 85% of the administered dose per gram localizing in the large intestine within the first hour, NiMOS resided in the stomach and small intestine for relatively longer duration. Following oral administration of CMV-betagal or EFGP-N1 plasmid DNA at 100 microg dose in the control and test formulations, the qualitative results presented in this study provide the proof-of-concept for the transfection capability of NiMOS upon oral administration. After 5 days post-administration, we observed transgene expression in the small and large intestine of rats. Based on these preliminary results, NiMOS show significant potential as novel gene delivery vehicle for therapeutic and vaccination purposes.
Bhavsar
Mayank D
MD
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, United States.
Amiji
Mansoor M
MM
D000284:Administration, Oral; D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D005753:Gastric Mucosa / Q000378:metabolism*; D005780:Gelatin / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D011091:Polyesters; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C016240:polycaprolactone; D005780:Gelatin; D004247:DNA; D001616:beta-Galactosidase