Evaluating gelatin based nanoparticles as a carrier system for double stranded oligonucleotides.
OBJECTIVE
Surface modified gelatin nanoparticles were tested as a potential carrier system for double stranded DNA and RNA oligonucleotides. The results will be discussed with regard to former experiments conducted with single stranded oligonucleotides.


METHODS
Gelatin nanoparticles were prepared by a two step desolvation method and surface modified by the covalent coupling of a quaternary amine to obtain a permanent positive net charge. Oligonucleotide loading was conducted in three different media applying 50 microg oligonucleotide per mg nanoparticles in total. Five batches of nanoparticles varying in size and zeta potential (zeta) were tested. The zeta potentials were determined under enforced ionic conditions in a 10 mmol sodium chloride solution at pH 7.0. The separation of unbound oligonucleotides and gelatin nanoparticles was achieved by centrifugation. Free oligonucleotide was determined UV-spectrophotometrically (260 nm) in the supernatant.


RESULTS
It could be shown that up to 50 microg nucleic acid per mg nanoparticles can be bound depending on the particle's zeta potential and the chosen incubation medium.


CONCLUSIONS
The results suggest that the proposed procedure allows a successful drug loading of double stranded oligonucleotides onto to the surface of accordingly modified gelatin nanoparticles.
Zillies
Jan
J
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Butenandtstrasse, Munich, Germany.
Coester
Conrad
C
D004247:DNA / Q000032:analysis / Q000138:chemical synthesis; D004337:Drug Carriers / Q000032:analysis / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005780:Gelatin / Q000032:analysis / Q000138:chemical synthesis*; D049329:Nanostructures / Q000032:analysis / Q000737:chemistry*; D009841:Oligonucleotides / Q000032:analysis / Q000138:chemical synthesis*; D012330:RNA, Double-Stranded / Q000032:analysis / Q000138:chemical synthesis
D004337:Drug Carriers; D009841:Oligonucleotides; D012330:RNA, Double-Stranded; D005780:Gelatin; D004247:DNA